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Trends in Neonatal Lung Pathology
Grace Francis Dícosta*, Milind Chincholikar+, Yoganand Patil**
 

Abstract

Neonatal pulmonary pathology merits particular study, since respiratory disorders remain a major cause of neonatal mortality and respiratory pathology is the commonest autopsy finding in neonates.
The present study was undertaken to examine the prevalence and type of pulmonary pathology encountered in neonatal autopsies. We compared two study periods 1989-91 and 1994 to note any changing trend. The Wigglesworth classification was utilized to classify deaths and the contribution of pulmonary pathology in each group was noted. 292 neonatal autopsies were analyzed. Pulmonary pathology contributed in a major way to neonatal mortality. It was the primary and secondary cause of death in 61.64% and 24.66% cases respectively and unfortunately the trend has not changed over a time interval. The most frequently encountered lesion was pulmonary haemorrhage 54.11% closely followed by pulmonary immaturity 52.25% both these leading causes did not show any changing trend. However it is heartening to note that, there was a sharp 50% drop in the incidence of hyaline membrane disease and bronchopneumonia, credit for which should go to the neonatologists. According to the Wigglesworth classification, the leading group as far as the cause of death was concerned was group III ‘Conditions associated with prematurity’, 50% but it was in group IV ‘Asphyxial lesions’-20-55% that pulmonary pathology contributed maximally to deaths 85% the main lesion being pulmonary haemorrhage.

 

Introduction

Over the last few years, both perinatal and neonatal mortality rates are reported to have declined considerably in many western countries, largely owing to improved medical care during this period of life. In the developed countries, the perinatal mortality rate is less than 10 per 1000 live births as compared to the alarmingly high rate of 60-120/1000 live births in India. About 1.5 million perinatal deaths occur every year in our country.2 Based on the available information and a review of literature, it is clear that 50% of deaths in infancy in India occur during the neonatal period. (Reddaiah and Nath 1975; Kumar, 1982).1 Hence knowledge of the spectrum of common neonatal disorders in the Indian context is important, as it helps in developing appropriate facilities and management protocol to improve neonatal survival.3 Since respiratory disorders remain a major cause of neonatal mortality and morbidity4 and respiratory pathology is the commonest autopsy finding among early neonatal deaths,5 neonatal pulmonary pathology merits particular study.
In the interpretation of neonatal lung pathology, two considerations are important. Because of interpretive limitations of histopathology, a clear understanding of clinical history is mandatory. The history should include the antenatal history with accurate gestational dates, and specific reference to such events such as PROM and intercurrent maternal infections; a detailed history of labour and delivery including reference to meconium staining of liquor and intrapartum foetal distress; post partum history with reference to the establishment of spontaneous respiration and annotations of all events in the NICU, including details of ventilation, pneumothoraces and septicaemic episodes.6
In addition, though it may appear paradoxical, many therapeutic advances have been associated with the emergence of lesions that hitherto had been extremely rare or unknown. These lesions are either adverse effects of therapy (iatrogenic disease) or consequences of partial ‘iatrogenic success’.7 There is a lot of overlap between the morphological changes seen in different clinico-pathological syndromes and iatrogenic effects. It is frequently difficult to say which changes are primary and which are due to the effects of treatment. However giving due consideration to history permits a reasonable assessment of the pathogenic mechanisms which have pertinence in an individual case.6

Material and Method

Two hundred and ninety two neonatal autopsies, performed at our institute during the study period, were reviewed. Of these 217 were performed during the period January 1989 to December 1991 and 75 were performed during the year 1994. Information on the mothers and their babies was obtained from a review of the patient’s hospital records. The following maternal and neonatal factors were recorded from the neonatology unit : mother’s blood group and VDRL status, past and present obstetric history including history of immunization, fever, dysuria, premature rupture of membranes, antepartum haemorrhage, pregnancy induced hypertension, diabetes mellitus, jaundice, any drug use; delivery notes including the presentation, the mode of delivery, nature of liquor and staining; infant’s sex, birth weight, gestational age, resuscitation required if any and the age at the time of death. Gestational age was based upon the menstrual date, an early ultrasound scan where performed and the use of the Ballard modification of the Dubowitz score, on every baby admitted to the NICU.


Autopsy was performed between 4 and 24 hrs after death, following the method described by Potter and Craig,1 Valdes-Dapena2 and Huff.3 External examination included a careful inspection to determine the maturity of the infant and the presence or absence of external anomalies. Morphometric measurements were made of the crown-heel length, the crown-rump length, the head, chest, and abdominal circumferences. All cavities were examined in situ to exclude or document various malformations. The thorax was opened under water to test for the presence of pneumothorax. The size and nature of any pleural effusion was noted. The state of inflation of the lung was recorded. The proximal airways were examined for the presence of any aspiration, especially meconium aspiration, or foreign body. The heart was separated from the lungs after looking for and ruling out any anomalous- cardiopulmonary vascular connections and emboli. For fixation, the lungs were inflated with 10 % formalin solution through the main bronchus, with a syringe, and left in a container of formalin for 48 - 72 hours. However this method was not utilized when hyaline membrane disease (HMD) was suspected, as inflation with formalin tends to expand the collapsed alveolar ducts and break up the membranes and hence a histopathological diagnosis is made impossible. In cases of suspected HMD, a note was made to look for lobular markings on the pleural surface, as these are absent in cases of HMD.
After fixation the lungs were weighed and the pleural surfaces examined for the presence of any pathology. Solid lesions, including consolidation, were felt for. Parasagittal sections of the whole fixed lung were cut using a long brain knife. The cut sections were examined with the naked eye and with the hand lens for the extent and type of any atelectasis, emphysema, pulmonary haemorrhage, consolidation, abscess etc. as well for evidence of meconium plugging of the bronchioles.

For histological study, at least one block was taken from each of the main bronchopulmonary segments and additional blocks taken from the lesion. Paraffin sections, 5 µ thick, stained with hematoxylin and eosin, were studied under the 10x, the 25x and the 40x objectives. Special stains were done when required.

In each case autopsy protocols, microscopic slides and clinical charts were analyzed with special reference to mortality related to birth weight and gestational age.

Regular clinico-pathologic conferences were held throughout the period of study for the purpose of evaluating the cause of death of each baby who died. The demographic data was limited to the frequency found among the cases studied

Results

A comparison of the contribution of pulmonary pathology either primary or secondary to neonatal mortality was made for the two periods of study i.e. 1989 – 91 and 1994, to ascertain if there was any change in the trend or pattern of the causes of deaths. 292 autopsies were performed over the entire period of study, 217 in the interval between 1989 and 1991 and 75 in the year 1994 (Table 1). In the first interval the primary or secondary cause of death was pulmonary in 87.56% cases, a similar high percentage of 82.66% was also noted in the year 1994. The non pulmonary causes of death in both the periods was correspondingly much lower i.e. 12.44% and 17.33% respectively. Overall, pulmonary pathology contributed in a major way to neonatal mortality 86.30% cases, either as a primary or secondary cause of death and the trend unfortunately has not changed over an interval of time (Table 1).
A further year-wise split up of the deaths attributable to pulmonary pathology, into primary and secondary causes, clearly indicates a consistent trend in all the years and in both the periods. Pulmonary pathology has been the primary cause of death in more than half the cases in both the periods i.e. 62.67% and 58.67% respectively and hence has contributed in a significant way to neonatal mortality. However it is less frequent as a secondary cause of death, 24.9% and 24% respectively (Table 1). For the entire period of study, pulmonary pathology accounted for the primary cause of death in 61.64 % cases, and for the secondary cause of death in 24.66% cases (Table 1).

The classification of Wigglesworth4 for neonatal deaths is utilized at our institute and the final cause of death is arrived at after joint clinico-pathological conferences are held with the clinicians. Over the entire period, the category which had the maximum number of cases was the category of ‘Conditions associated with prematurity’ - III -50%, which includes hyaline membrane disease (HMD), immaturity alone, intraventricular haemorrhage, early onset sepsis, necrotizing enterocolitis, patent ductus arteriosus etc. This trend is seen in both the periods though there is a slight decline in the percentage of cases in the year 1994 - 41.33% compared to the earlier interval of 1989- 91 - 53%. This indicates a need for improvement of NICU care. ‘Lethal congenital malformations –II ’ were the least frequent as the primary cause of death -6.50%, though there is a slight increase in 1994 - 8%, compared to the previous period of 1989-’91 - 5.99%. The other two categories of ‘Asphyxial conditions at birth – IV’ and ‘Others – V’ fall in between these two and are almost equal in frequency for the entire period - 20.54% and 22.97% respectively, however when comparisons between the two interval periods are drawn, Group IV shows a significant increase, indicating deterioration in obstetric care; whereas Group V shows a slight decrease, it is difficult to attribute this to any one single cause, as the category includes several causes and is literally a wastebasket category (Table 2). Pulmonary pathology contributed to the primary cause of death in 61.64 % cases for the entire period, the contribution was slightly higher 62.67% in the first interval (1989 - 91) compared to the second period (1994) - 58.67% and this holds true for all the groups. In group IV – i.e. ‘asphyxial lesions at birth’, pulmonary pathology has contributed in major way – 85% cases, and this is mainly due to pulmonary haemorrhage, either massive (Fig.1) or focal, which is commonly associated with birth asphyxia. In Group II -i.e. ‘Lethal congenital malformations’ the contribution of pulmonary pathology was the least - 26.32%, the main lesion being pulmonary hypoplasia (Fig. 2). The other two groups - Group III and V, were in between these two, as far as contribution of pulmonary pathology is concerned, and it was almost equal in both these groups -57.53% and 59.70%; in the former, immaturity (Fig. 3) of the lung alone and HMD (Fig. 4), and in the latter pneumonias (Fig. 5) headed the list (Table 2).

Comparison of the incidence of the different pulmonary pathological lesions over the two periods, reveals a fairly static pattern in the majority of cases. Certain exceptions however are noticeable. The incidence of HMD (Fig. 4), bronchopneumonia (Fig. 5) and

Fig. 1 : The photograph showing lungs appear dark red solid and the confluent haemorrhage has involoved all the lobes of both the lungs.

Fig. 2 : The photograph of pulmonary hypoplasia showing  the small lungs with a decrease in weight and volume, without the absence of any of the lobes. The inferior surface of the lungs is not in line with the apex of the heart. This case was a 30 weeks gestation neonate with cystic renal dysplasia  - Potter’s  type-II

Fig. 3 :Photomicrograph of immature lung showing canalicular stage. (H & E,x100)

Fig. 4 : Photograph of hyaline membrane disease showing lungs appear airless, solid or liver-like with loss of lobular markings. (H & E, x100)

Fig. 5 : Photograph of early stage bronchopneumonia showing a mixed inflammatory exudates in the bronchi and surrounding. (H & E, x100)

abscess formation show a significant - 50% drop in the period 1994 compared to the period 1989-1991; however the other types of pneumonias, namely interstitial and lobar, though much less frequent, do not reveal much of a change in incidence. In the asphyxial lesions encountered, the incidence of pneumothorax shows a drop - 8.29% to 1.33%, with a corresponding decrease in the incidence of meconium aspiration from 4.61% to 1.33%. However there is a surprising rise in the incidence of amniotic aspiration - 9.68% to 17.33%, though the two conditions are directly related to each other. Heading the list of pulmonary pathological lesions is pulmonary hemorrhage - 54.11% cases, either focal or massive (Fig. 1); this shows consistently the highest % in both the periods - 52.54% and 58.66%.This condition is associated with birth asphyxia and clearly indicates, an improvement in obstetric care is required. Closely following pulmonary hemorrhage is pulmonary immaturity (Fig. 3) 52.05%, where immaturity alone is the cause of death and pulmonary immaturity contributes in a significant way. This lesion is also consistently high in both the periods of study - 52.07% and 52% respectively. By contrast, ‘Lethal congenital pulmonary malformations’ encountered were few – 2.05%.In fact the only lesion encountered in this group was pulmonary hypoplasia (Fig. 2), commonly associated with cystic renal dysplasia. Broncho-pneumonias (Fig. 5) and HMD (Fig. 4), lie intermediate in frequency -22.26% and 17.47% respectively (Table 3).

In both the periods the maximum number of deaths occurred in the (1 - 7 day) period -70.89%, followed by the 8 - 28 day period -15.75 % and the least number of deaths were in the < 24 hr period - 13.36%. An opposite trend is observed when taking into consideration pulmonary pathology as the primary cause of death during the two periods. In the first period, 1989-1991, as the age increases the contribution of pulmonary pathology to death decreases and during the period 1994, the reverse holds true. It would be worthwhile noting that during the first period, for the < 24 hrs neonates, it was pulmonary immaturity (Fig. 3) and HMD (Fig. 4) that contributed significantly to the cause of death, both of which are likely to lead to early neonatal deaths.

In the period 1989-1991, the maximum number of deaths - 63.51% occurred in neonates of gestational age 28 - 33 wks, whereas both, the very low gestational age < 28 weeks and term neonates fared equally well - 18.89% and 17.51% respectively. However the trend changes in 1994, where the neonates of higher gestational age fare badly, the percentage of deaths being almost equal in both categories i.e. 28 - 36 weeks - 37.33% and the ³ 37 weeks - 40%; both the percentages are higher and almost double the percentage of neonates of very low gestational age i.e.: < 28 wks -22.67%. As far as the contribution of pulmonary pathology is concerned, a similar trend is noticed in both the periods i.e. as the gestational age increases, the percentage of contribution of pulmonary pathology to death correspondingly increases, and this is more conspicuous in the year 1994. An explanation for this is that larger babies are more prone to birth asphyxia, which produces pulmonary haemorrhage, which incidentally has been the leading pulmonary pathology in our series. On the whole, the contribution of pulmonary pathology to deaths in the period 1989-’91 is slightly higher - 62.67%, compared to the year 1994 -58.67%.

In both the periods, the maximum number of deaths occurred in the very low birth weight (VLBW) neonates £ 1500 gms- 60.51 % and 50.67% respectively. In 1989-’91, this was followed by the low birth weight (LBW) neonates 1501-2500 gms -26.73% and the least number of deaths occurred in the normal birth weight (NBW) neonates -11.98%. However in the year 1994, the trend was reversed for these two categories, the figures being 20% and 29.33% respectively. However for both the periods, it was VLBW - 57.88%, followed by LBW - 25 %, followed by NBW - 16.44 %. Another observation is that both, in the VLBW and LBW categories, the number of deaths have reduced, whereas the reverse holds true for NBW neonates. As far as the contribution of pulmonary pathology to death is concerned, in both the periods the contribution was maximum in the NBW neonates - 73% and 90.11% respectively. This was attributable to the high incidence of pulmonary haemorrhage, associated with birth asphyxia that is common in term neonates.

As far as relationship between the presence of risk factors and HMD is concerned, the neonatal risk factors significantly associated with HMD in both the periods were, prematurity - 78.57% and 75% cases, and LBW - 88.10% and 87.5% respectively.

No sex preponderance was noted. Maternal risk factors like ante partum haemorrhage (APH), pregnancy induced hypertension (PIH) and diabetes did not appear to be significant, in fact we did not have a single case of diabetes mellitus. Surprisingly, most of the cases were normal deliveries - 92% and there were only 8% cases associated with LSCS.

When an attempt was made to subclassify the various stages of HMD, in both the intervals, and most of the cases fell in the acute stage - 83.33% and 87.5%, a few cases fell into the healing stage - 16.67% and 12.5%. There were no cases that fell into the transitional or chronic stage. Thus most of our neonates succumbed in the early stages of HMD, and the effects of oxygen toxicity with evolution to broncho-pulmonary dysplasia did not prove to be a problem.

Discussion

The lung plays a central role in relation to the pathology of the neonatal period as it reflects or determines the ability of the foetus to make the transition from an aqueous to a gaseous environment and respiratory pathology is the commonest autopsy finding among neonatal deaths. Knowledge of the spectrum of common disorders helps in developing appropriate facilities and management protocols to improve neonatal survival, while data about the incidence and severity of the disorders helps to identify the priorities.

The overall contribution of pulmonary pathology to neonatal mortality in the entire period of study, either as a primary or secondary cause of death (Table 1), was as high as 86.30 % and this trend has not changed significantly over an interval of time. It was 87.5% in the period 1989-1991, and 82.66% in the year 1994. However, if pulmonary pathology is considered as the primary cause of death, the figures are lower, i.e. 61.64%. 62.67% in the period 1989-1991 and 58.67% in the year 1994. Yet our figures are much higher than the figures in the western literature. Tock (1964)5 encountered pulmonary pathology in 25% of his cases. Indian literature however reveals figures which are more comparable with our figures. Athavale et al (1969)6 - 62.67%, Tibrewala et al (1975)7 found a higher contribution of pulmonary pathology to the cause of death 88.8%.

We have utilized the well-recognized classification of Wigglesworth (Table 2) to classify our neonatal deaths as it is action oriented and of immense value to our clinicians. Utilizing this classification the leading category was ‘Conditions associated with prematurity –III’ - which accounted for 50% of neonatal deaths. This was followed by an almost equal percentage of ‘Asphyxial conditions at birth – IV’ and ‘Others – V’ category - 20.54% and 22.97% respectively. The least frequently encountered category was ‘Lethal congenital malformations –II’ - 6.51%. In western literature, ‘Conditions associated with prematurity’; followed by ‘Lethal congenital malformations’, appear to be the leading causes of death, whereas ‘Asphyxial lesions’ and ‘Sepsis’ are less frequent.

Our data tends to correlate better with western literature compared to Indian literature as far as the final leading cause of death is concerned. Most of the western series reveal prematurity and conditions associated with prematurity to be the leading cause of, death. Valdes-Dapena 19708 encountered it in 12.57% cases. Hein et al 19819 198610 found it in 41.7% and 35.48% cases in his two series. However when it comes to ‘Lethal congenital malformations’ the data is at variance. Except for the series of Hein et al (1986)10 where congenital malformations occurred least frequently 5.58% as in our series 6.51%. Other western series reveal it to be the second leading cause of death. Valdes-Dapena 19708 - 5.79% and Hein et al 19819 - 21.1%. ‘Asphyxial lesions’ and ‘sepsis’ usually follow the above mentioned two leading causes of death in western literature, Valdes-Dapena 197019 and Hein et al 1981,9 whereas in our series , they are almost equal in frequency and are sandwiched between these two causes i.e. the leading cause, ‘Conditions associated with prematurity’ and the least frequent cause, ‘Lethal congenital malformations’. The 1986 series of Hein et al10 almost corresponds to our series.

As far as Indian literature is concerned, except for the series of Jain et al 198411 and M. Singh 199112 - which cite ‘Immaturity’ and conditions associated with it to be the leading cause of death, 65.4% and 35.81% respectively, with ‘Asphyxial lesions’ following it in 17.6% and 20.49% cases respectively, most of the Indian literature cite either ‘Asphyxial lesions’ or ‘Infections’ to be the leading cause of death. The series where ‘Asphyxial lesions’ topped the list were those of Bhakoo et al 1975,13 Joshi et al 197914 43%, M.Singh 199112 - 59%. In most of these series, ‘Conditions associated with prematurity’, was the next in frequency, and ‘Congenital malformations’ was least frequent. Thus compared to the rest of the Indian workers ‘Conditions associated with prematurity’, and ‘Asphyxial lesions’ appear to have reversed their positions in our series, as the first and second cause of death, but congenital malformations remained least frequent. In two series however of Tibrewala et al 19757 and Bannerjee et al 1975,13 ‘Infections’ headed the list of the causes of death - 41.57% and 21.2% respectively, this was followed by ‘Congenital anomalies’ -25.84% and 16.14%, ‘Asphyxial/Traumatic lesions’ - 17.47% and 15.2% , and lastly ‘Conditions associated with prematurity’ -11.20% and 9.6%. The causes of death run parallel in these two series but are at variance with the rest of the Indian literature, including our series.

As far as contribution of pulmonary pathology to death is concerned in the individual categories of Wigglesworth’s classification (Table 3), in Group IV i.e. ‘Asphyxial lesions’, the contribution was maximum i.e. 85%. This was mainly due to massive and focal pulmonary haemorrhage. The contribution of pulmonary pathology was least in Group II i.e. ‘Lethal congenital malformations’ -26.32 %; all these cases were of pulmonary hypoplasia. In the other two categories, which fall intermediate in position, the contribution is almost similar and also quite significant. In Group III i.e. ‘Conditions associated with prematurity’, it was 57.53% - pulmonary immaturity and HMD being responsible for a large percentage. In Group V it was 59.7%. In this group, pneumonias contributed significantly.

A look at the various pulmonary pathological lesions (Table 3) encountered over the entire period reveal data which is more comparable to Indian than western literature, pulmonary haemorrhage was the most frequently encountered lesion - 54.11%; these cases were seen most often when there was a history of birth asphyxia. Massive pulmonary haemorrhage (Fig. 1) was seen in only 17.47% cases, this figure is comparable to that of Tibrewala et al 19757 - 4.8% but is low compared to that of De Sa et al 1970 which is 41.4%, even though he states that is a decline in incidence from the year 1948 to 1965. De Sa DJ indicates the importance of obstetric factors in the production of massive pulmonary haemorrhage (MPH)15 the slight increase in our rate of MPH may reflect poorly on the obstetric practices. The next most frequently encountered pathology is immaturity of the lung (Fig. 3), when immaturity alone has been the cause of death - 52.05%, following this is pneumonia (Fig. 5), which accounted for 22.26% cases, out of which the maximum were bronchopneumonia -17.81%. This figure is comparable or slightly less than Indian autopsy data, where 26%- 46% of neonatal deaths are associated with pneumonia- Athavale et al 1969,6 Bannerjee et al 1975,13 Tibrewala et al 1975.7 In western literature earlier series reported a fairly high percentage of pneumonia; MacGregor 193916 - 31.7% out of which 15% was bronchopneumonia. However more recent literature indicates a low percentage of sepsis, and inflammatory lesions in general-Valdes-Dapena 19708- 39%, and Hein et al 19819 -12.4% and of pneumonia in particular - Hein and Brown 19819 -12.4%.

Hyaline membrane disease (HMD) (Fig. 4) featured next and accounted for 17.47% cases. Indian literature reveals a much lower Indian literature reveals a much lower incidence of HMD compared to western literature. In fact Indian studies have uniformly concluded that HMD is a relatively uncommon cause of neonatal death,- Banerjee et al 1974.13 In fact Tiberewala et al 19757 have found it in only 1.9% cases. However M.Singh12 tends to differ from this notion and feels that it is not that relatively uncommon. He found it in 13.7% of cases. We tend to agree with him; in our series it was higher i.e. 17.47%. However these figures are very much lower than the western figures which may vary from 30.1% to 52.9% - Doshi et al 1980.17 While Indian studies showed a persistently lower rate of HMD compared to western literature, both Indian and western authors have documented a decreasing incidence of HMD. This was seen in our series also, the rate dropped from 19.35% in 1989-1991 to 10.67% in 1994.

Lung abscess was found infrequently: 4.11%. There were totally 12 cases found; 10 in 1989-’91 and 2 in 1994. In 1989-’91, 5 were pseudomonas abscesses, two of fungal aetiology one Candida albicans and one Aspergillus fumigatus, one Klebsiella and two could not be typed. In 1994, one was due to Pseudomonas and the other due to Klebsiella infection. The incidence of abscess formation was also very low in the series of Tibrewala et al 19757 -0.2% Pulmonary hypoplasia (Fig. 2) was seen very infrequently - 2.05% cases and was the only congenital anomaly encountered; it accompanied a number of congenital malformations, the commonest being cystic renal dysplasia -2/6 cases - 33.3%. Page and Stocker 198218 also found a similar low incidence of pulmonary hypoplasia - 1.8%.

Age-specific mortality rates are highly important in decision making. When age at death was taken into consideration, the early neonatal period of 0 - 7 days was the most vulnerable, the maximum number of deaths - 84.25% , occurred in this period. In Indian literature, this figure is comparable to that of Tibrewala et al 19757 - 77%, but higher than the figures of Athavale et al 19696 -58%. In western literature, A.G.S.Philip19 reports a lower incidence of 75.5%, probably indicating better NICU facilities in the west. However if this early neonatal period is split up into < 24 hrs and 1 - 7 days, surprisingly in our data the former indicated a lower percentage of mortality -13.36%, compared to the latter -70.89%; this is at variance with both Indian and western figures. Tibrewala et al 19757 -found 57% mortality in < 24 hours, and 43% in > 24 hours neonates; and A.G.S. Philip 199519 encountered 47.9% mortality in < 24 hours neonates and 27.8% in 1-7 day neonates. As far as the contribution of pulmonary pathology to deaths is concerned it is worthwhile noting that as the survival period increases, the contribution decreases. Pulmonary immaturity has contributed significantly to early neonatal deaths.

When gestational age is taken into consideration, most of the fatalities were preterm neonates £ 36 weeks - 76.71% ; this holds true for all the indian and western studies. M. Singh 199112 encountered preterm deaths in as high as 86.05% cases. In western literature, Copper et al 199320 also encountered a high percentage of 83%. If the gestational age is split into three categories, the maximum number of cases falls in the 28 -36 week category -56.85 %, followed by the > 37 week category, and the < 28 week category 19.89%. M. Singh 199112 also reported the highest percentage in the 28 - 36 week category -64.19%, but this was followed by the < 28 week category -21.86% and ³ 37 week category -13.95%. As far as the relationship of the contribution of pulmonary pathology to mortality in the different gestational age groups is concerned, the contribution increases as the gestational age increases; this is probably attributed to the fact that a large percentage of pulmonary pathology is pulmonary hemorrhage, which is usually seen in neonates of higher gestational age, in association with birth asphyxia.
When all the neonatal deaths were split up into the different birth weight categories the largest number of cases were in the VLBW category of £ 1500 gms -57.88%, followed by the LBW category < 2500 gms. Our findings are consistent with most Indian and western authors. When only two categories of LBW and NBW are considered, the LBW category accounted for 82.88% deaths and the NBW for 16.44% deaths. The series of V.V. Joshi 197914 also reveals a high percentage of LBW neonates i.e. 77.5%, which is however lower than our figure of 82.88%; his percentage of NBW is correspondingly lower than ours, 29.8% v/s 16.44%. However in the LBW category, his percentage of VLBW neonates is lower than that of the LBW neonates i.e. 32.8% and 44.7% respectively, whereas the reverse holds true in our cases. M. Singh 198212 and L. Jain 198411 also reported a percentage of LBW neonates similar to Joshi i.e. 75.5% and 77.7% respectively. In fact in the series of L.Jain 11, the further split up of LBW reveals figures similar to ours i.e. 56.3% for VLBW and 21.4% for LBW.

In western literature, the scenario is similar. Valdes-Dapena 19708 found the incidence of LBW deaths to be as high as 89%, whereas the NBW neonates accounted for only 11% deaths. Again his percentage of VLBW deaths is higher than that of LBW deaths, 51% and 38% respectively, similar to our findings. A.G.S.Philip 199519 found a high neonatal mortality rate in the VLBW neonates, 22/1000 live births, compared to 2/1000 live births in the LBW categories and 3/1000 live births in the NBW categories.

Another observation made is that the percentage of VLBW and LBW deaths has decreased in both the periods of study, by 10% in the VLBW category and 6.73% in the LBW category. M. Singh 199112 reports a drop in the percentage of deaths of LBW neonates by 10.8%. This is probably due to an improvement in the NICU facilities. By contrast the percentage of deaths of NBW has increased by 17.35% probably indicating deteriorating obstetric care. Also as far as the contribution of pulmonary pathology to the primary cause of death is concerned, it has decreased in both the VLBW and LBW categories but increased in the NBW category. This is probably related to the increase of the number of NBW neonates in the year 1994, who are more prone to birth asphyxia which usually leads to massive pulmonary haemorrhage, which has contributed to the increased incidence of pulmonary pathology contributing to death in this period.

When the relationship between the presence of risk factors and HMD were considered, the risk factors which were significantly associated with HMD were LBW and prematurity, which were fetal risk factors. An association between preterm delivery and HMD has been reported in literature. In our series prematurity was present in 78% of the cases of HMD; other Indian series Patil et al 198321 have reported an even higher incidence of 81.03%. A significant association has also been found in western literature; Fredrick and Butler22 found a decrease in the percentage of HMD from 23.7% to 0.9% as the gestational age increased from 28 - 30 weeks to 35 - 36 weeks. LBW infants are at an increased risk for the development of HMD.13,14 We also support the contention, as 88% of our cases of HMD were LBW. Patil et al 198327 also noted that as the birth weight increased, the incidence of HMD decreased. In western literature also similar observations have been made – Avery et al 1968.23 In fact the neonatal death rates / 1000 live births with HMD have shown a decrease as the birth weights increase.23 Though the general contention is that the male sex, second of twins, diabetes, and LSCS increase the likelihood of HMD, we have not found it significant. The male:female ratio was 1:1, twins were found in only 12% of the cases, diabetes was not present in a single case and LSCS delivery was done in only 8% cases. Other Indian authors were also at a loss to establish a relationship with these factors; Patil et al 198321 found a male : female ratio of 1.1 :1 , caesarean section in 10.3% cases, twin deliveries in 5.2 % and diabetes in 5.2% cases. In western literature, diabetes was associated with a significant effect only at term. As far as caesarean section is concerned there is a four fold increased risk of HMD with caesarean section especially in premature neonates, while caesarean section was also associated with a higher incidence of respiratory distress syndrome (RDS), but the increase was significant only at gestations of > 34 wks.

All the cases of HMD i.e. 50 cases were subclassified into the acute, healing, transitional, and chronic stage. The acute stage was the most frequently encountered i.e. 84% cases, followed by the healing stage - 16% cases. We did not find any case of the transitional or chronic stage. Our findings are similar to those of Patil et al 198321, he also subclassified HMD into the various stages. They found the acute stage in 69% cases, the healing stage in 27.6% cases and the chronic stage in 1.7% cases. The later stages are probably not encountered, since the neonates in our set-up do not survive the acute period and oxygen therapy is not favored.

When the cases of pneumonia were subclassified based on the histological distribution of the inflammatory infiltrate, most of our cases were bronchopneumonia -80%. In western literature however a lower incidence of bronchopneumonia has been found i.e. 46.3% - A.R. Macgregor 193916 in fact as discussed earlier the overall incidence of pneumonia is lower in the west, because of superior methods of control of infection.

Conclusions

Two hundred and ninety two neonatal autopsies were analyzed over the entire period of study, 217 in the period 1989-1991 and 75 in the year 1994. In the first interval 1989 - ’91 pulmonary pathology contributed to the primary or secondary cause of deaths in 87.5% cases and in the second period of 1994, to a similar high percentage of 82.66% cases. The contribution of pulmonary pathology to the primary cause of death was lower in the two periods 62.67% and 61.64% respectively. Thus pulmonary pathology has contributed in a major way to neonatal mortality -86.30% cases, either as a primary or secondary cause of death and the trend unfortunately, has not changed over an interval of time. Our findings are more compatible with Indian than western literature. When all the neonatal deaths were classified according to Wigglesworth’s classification, ‘Conditions associated with prematurity’- Group III was the leading group - 50%, and ‘Lethal congenital malformations’ Group II -6.51% the least frequently encountered group. The other two groups of ‘Others’ - Group V and ‘Asphyxial lesions at birth’ - Group IV were intermediate in position - 22.95% and 20.55% respectively. Amongst all these groups, it was in Group IV that pulmonary pathology contributed maximally to deaths - 85%, the main lesion being pulmonary hemorrhage which was frequently seen in association with birth asphyxia. The most frequently encountered pulmonary pathologic lesion was pulmonary haemorrhage - 54.11%, this was either focal or massive and this trend does not change over a period of time, indicating that an improvement in obstetrics care is required as this lesion is frequently seen in association with birth asphyxia. Closely following pulmonary haemorrhage is pulmonary immaturity -52.25% cases, which again does not show any changing trend, indicating that an improvement in NICU facilities for the care of such premature neonates is required. There is however a significant - 50% drop in the incidence of HMD and bronchopneumonia as causes of death; credit for this should go to the neonatologist. Congenital lethal malformations were least frequently encountered 2.05% cases, the only lesion being pulmonary hypoplasia. The maximum deaths were early neonatal deaths 1 - 7 days - 84.25% , low gestational age (< 36 weeks) deaths - 76.71% and low birth weights (< 2500 gms) deaths - 82.88 %. Pulmonary pathology contributed more significantly to early neonatal deaths, < 24 hrs - 66.67%, and 1-7 days - 63.29 %; deaths of normal gestational age (> 37 weeks) - 70.59% and normal birth weight (> 2500 gms)- 81.29%. In the latter two instances it is probably pulmonary hemorrhage that has contributed to asphyxial deaths in term babies. Hyaline membrane disease was significantly associated with fetal risk factors like prematurity - 78% cases and low birth weight - 88% cases. There was no sex preference. Twin pregnancies, caesarean section and diabetes mellitus did not seem to be contributory risk factors. Most of our cases of HMD were in the acute stage - 84%. There were only 16% cases in the healing stage and none in the transitional and chronic stages, indicating an early mortality in HMD and little experience on the effects of oxygen toxicity, which is usually associated with the later stages. Though there is a significant - 50% decrease in the incidence of pneumonia when the two periods are compared, in both periods it was bronchopneumonia that dominated the scene - 80% cases. Though, there has not been any major change in the trend of the contribution of respiratory pathology to neonatal deaths in the two periods of study, including the contribution of the leading pulmonary pathology i.e. pulmonary haemorrhage which remains persistently high, it is heartening to note that there is a sharp - 50% decrease in the incidence of HMD and bronchopneumonia in the two periods of study, indicating that the neonatologist are one up on the obstetricians.

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*Associate Professor, **Resident Pathologist, Department of Pathology, Grant Medical College, Byculla, Mumbai-8; **Pathologist, Al- Obaid Hospital, Saudi Arabia.

 
 
DIVIDING THE SEXES

Men seem to have a 50% higher risk than women of recurrent venous thromboembolism after stopping anticoagulant treatment’.
Venous thromboembolism, consisting of deep-vein thrombosis and pulmonary embolism, is a potentially fatal disorder with an estimated annual incidence of 0.1% in white populations. Simon McRae and colleagues did a meta-analysis of six prospective cohort and nine randomised trials in which patients were treated with anticoagulants for at least 1 month, and followed-up for recurrence after treatment was stopped. The analysis showed that men have about a 50% higher risk than women of recurrent thrombosis and that this increase is consistent across different subgroups of patients with venous thromboembolism. In a Comment, Vittorio Pengo and Paolo Prandoni state that it is too early to rely on the patient’s sex when determining the duration of anticoagulation in patients with idiopathic venous thromboembolism, and suggest further prospective studies are needed before a firm recommendation can be made.

Lancet, 2006; 342; 371.

 
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