Genetics Laboratory, School of Health Sciences, University of Pune, Pune 411 007, India.
Correspondence: Anita Kar PhD, Reader in Health Sciences, School of Health Sciences, University of Pune, Pune 411 007, India. E-mail: dranitakar{at}rediffmail.com
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Abstract |
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Methods The study was a retrospective cohort analysis from pedigrees collected from an earlier survey on haemophilia in Maharashtra. Pedigree data were manually defined into families with or without experience of haemophilia. Family size was defined as the number of live births per woman as documented in the pedigree. The data were analysed using Microsoft Excel package (version 2000) and SPSS package (version 10).
Results Family size of obligate carriers who were daughters of patients was significantly less than the family size of obligate carriers who reported haemophilia in a brother or maternal relative (z = 7.14, P < 0.001). As compared with parents from an older generation, a significant reduction in the number of children born to younger families with haemophilia was observed, irrespective of family history of the condition. In families with history of haemophilia, there was no significant reduction in the number of families with more than one affected son in between two generations of parents (2 = 1.43).
Conclusions The results revealed a reduction in size of families with haemophilia over a generation, which possibly reflected the reducing fertility trends observed in the Indian population. Reduction in the number of children born to women with a haemophilic father suggested a comprehension of father to daughter transmission of haemophilia. This was not true when relatives other than the father were affected. The lack of significant reduction in the number of families with history of haemophilia of having more than one affected son may suggest a compensatory response to the high mortality associated with the disorder in India.
Accepted 21 October 2002
With the backdrop of a major burden of preventable infections, malnutrition, a burgeoning population, and lack of resources, hereditary disorders are not a public health priority in India. National data on prevalence and types of genetic disorders and birth defects are unknown. Information on certain select disorders, primarily the haemoglobinopathies, is available from small studies.110 Data on the burden of specific genetic disorders on individuals, families, and society, and studies on mortality, morbidity, quality of life, and utilization of the health care system are unavailable.11
This study focused on haemophilia, a sex-linked bleeding disorder that affects 46/100 000 males worldwide.1,12 Haemophilia takes an exceptional toll on the patient and family in India, since treatment with anti-haemophilic factor (AHF) is beyond the reach of most families and is only used in times of medical emergencies. As a consequence, patients suffer progressive crippling disability, which adds to the poor quality of life. With extreme economic deprivation, families have no other option but to use the less-expensive blood and blood products, enhancing the risk of transfusion-related infections.
Population data on haemophilia are unavailable in India except for our earlier survey13second most populous State in the country.14 The objective of the study was to profile the haemophilia situation in the State, specifically to determine the total number of cases, the trends in case registrations, and to document the impact of the available haemophilia care services on haemophilia trends in the State. The study led to the identification of a total of 2192 known patients in the State, giving an observed period prevalence of 2.26/100 000 over a 10-year period. Geographical distribution revealed clustering of cases around three haemophilia clinics, which catered for all cases during the period 1989 to 2000. Case registrations were significantly absent from large areas where haemophilia care services had not been extended. The data revealed that there had been a 91% decrease in the number of new cases being registered over the 10-year period. In keeping with this profile of service delivery, clinico-demographic data of patients suggested that the longevity of severe patients was less than 25 years.13
In India, haemophilia care services are delivered by a voluntary organization whose primary objective is to provide AHF to patients at subsidized cost. Haemophilia education for patients and families is a recent phenomenon, established after the haemophilia societies came into operation, which was after 1989 in Maharashtra. Genetic counselling services including prenatal diagnostic services are unavailable. The transmission of haemophilia is complex since it can either appear de novo in a family, or be transmitted from an affected patient through his daughter to a grandson (Figure 1a) or be transmitted from a carrier mother through her daughter to the grandson.12 With poor literacy rates (65% for both sexes, and 54% for women14), and the dubious role of women in reproductive decision-making, there is no data available on whether knowledge of the hereditary nature of haemophilia results in modification in reproductive behaviour. Investigations on hereditary disorders in India are challenging since family history is a sensitive issue. This is especially true in the case of haemophilia, where it has gender-sensitive implications, since haemophilia is transmitted to the son from the mother. Furthermore, in the absence of psycho-social or genetic counselling services, the ethical aspects of a more qualitative approach towards analysing the impact of family history on reproductive decision making processes becomes pertinent. Thus, this study used pedigree data to determine whether family history of haemophilia affected the number of children being born to families reporting haemophilia in Maharashtra, India.
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Materials and Methods |
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Of the 1467 case papers, family history could not be ascertained for 501 cases and 691 did not report haemophilia in the family. Of the remaining 275 cases, family history of the condition was recorded for 189 cases. Pedigrees were also available for 469 out of 691 families without haemophilia in earlier generations.
Measures of impact of past history on family size
Impact of family history on family size was determined through a retrospective analysis based on pedigree data. Family history was defined as affected relative(s) in earlier generations of the patient, indicating that the mother had experienced the consequences of haemophilia in a family member. The term pedigree is used to represent the shorthand genetic history of haemophilia in that family as reported by the patient/family member. Family size was calculated as the number of live births per woman.
The available pedigrees were defined into 996 nuclear families as explained in the legend to Figure 1. Of these, 353 families had reported haemophilia in an earlier generation, implying that the mother had experienced haemophilia in a family member (Figure 1a
). The remaining 643 families had one or more affected sons but had not reported haemophilia in any other family member in the earlier generation (Figures 1b
, 1c
). The former families were categorized as families with history, whilst the latter group constituted families without history of haemophilia as explained in the legend to Figure 1
. The number of children born to each category was compared to determine the impact of family history on reproductive choices.
By definition, obligate carriers are daughters of affected fathers, or mothers with either two affected sons, or one affected son and affected maternal relatives, or mothers of daughters with affected sons.12 From pedigrees, mothers were categorized into two groups. The two groups classified as having history of haemophilia were: (a) women who were daughters of haemophiliacs, (Figure 1a, III2), and (b) women with affected maternal relatives (Figure 1a
, II3). Women without history of haemophilia included mothers of haemophiliacs without affected relative in earlier generations (Figures 1b
, 1c
). The family size of these three cohorts was analysed by determining the number of children born to each category of women.
Using the reported age of the patient at the time of registration, parents were categorized into two groups. Group I represented those parents where the age of the patient at the time of registration was above 25 years. Group II constituted those parents where the patients age at registration was between 8 and 12 years. The number of children born to group I families was compared with the number of children born to group II families.
In order to determine whether family history of haemophilia influences the number of affected sons born to a family, parents were categorized into two groups. Group III represented those parents where the age of the patient at the time of registration was over 20 years. Group IV constituted those parents where the patients age at registration was below 10 years. The number of affected sons born to both groups was compared against their family history status.
All data were analysed using either Microsoft Excel package (version 2000) or SPSS package (version 10).
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Results |
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Family size of haemophiliacs
Only 10% of families reported a haemophilic grandfather (Table 1, ii). Analysis of pedigree data revealed that over the 10 years, 154 out of 2192 patients had married. Of these, 27% were patients with severe haemophilia A. Our earlier data13 had shown that only 25% (i.e. 173/689) of severe patients survived after the age of 20 years. Thus, taking this into account, it appeared that 24% (41/173) of the severe haemophilic population that survived beyond 20 years had married over the 10-year period. Pedigrees revealed that these 154 married patients had 187 sons and 244 daughters (Table 2
, i). The latter were therefore obligate carriers of the disorder. Family size of the haemophilic population was thus 2.9 ± 2.3.
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The number of children born to women who reported haemophilia in a brother or other maternal relative (n = 256, family size 3.0 ± 1.5) (Table 2, iii) was significantly more than the family size of obligate carriers whose father had haemophilia (z = 3.1, P < 0.05). These data suggested that the reproductive decision-making was influenced when a daughter had experienced haemophilia in her father. However, when the affected man was a brother or another maternal relative, these experiences did not affect the family size.
Family size in older versus younger generation of haemophilic families
In order to determine whether there had been a reduction in the number of children born to families with haemophilia, the family size of older versus younger parents was compared (Table 3a, group I versus group II). Analysis of these data revealed that there was a reduction in the number of children of both sexes born to group II (younger) versus group I (older) parents (Table 3a
). The reduction was significant irrespective of family history of haemophilia (MannWhitney U test, z = 3.086, P < 0.05 for males and z = 2.345, P < 0.05 for females).
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Discussion |
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KEY MESSAGES
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Acknowledgments |
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References |
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