Congenital malformations and birth weight: a family perspective

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Congenital malformations and birth weight a
family perspective

• Dr. Kari K.Melve
• Department of Public Health Primary Health Care
• University of Bergen, Norway
• October, 2002

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Why is it fascinating to study families?

• Families constitute small populations with
  shared genetic and environmental features
• Dependencies between family members have
  implications for risk assessment (for instance of
  adverse pregnancy outcome)

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Why is it fascinating to study birth defects?

• Birth defects account for a large proportion of
  perinatal and infant mortality
• The etiology of birth defects is in large not
  known
• 25 - 30 of major birth defects
  may be attributed genetic factors

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Background for this study

• There is a large and significant correlation
  between siblings birth weights
• Low birth weight tends to recur in sibships

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• In general, infants with congenital malformations
  have lower mean birth weight than infants without
  malformations

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• Growth restriction may be primary, predisposing
  the fetus for malformations
• or secondary to the malformations
• ...or coexist with the malformations, and have
  common underlying causes

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Objective

• To study birth weight of malformed infants
  siblings
• ..and compare with birth weight of infants in
  families without any registered malformations

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Materials and methods

• Data were from the Medical Birth Registry of
  Norway from 1967 to 1998
• Infants were linked to their mothers through the
  unique personal identification number

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Study population

• 551,478 mothers with at least two infants and
• 209,423 mothers with at least three infants
• These family sets were not mutually exclusive

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• Familes were grouped according to whether and in
  which birth order an infant was registered with a
  birth defect
• Families where none of the infants had a birth
  defect were used as control families

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Table I
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Classification of birth defects

• Categories of defects were defined on the basis
  of ICD-8, providing 24 groups of isolated defects
• Multiple defects were combined in a separate
  category

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Analyses

• We compared mean birth weight (BW) and
  gestational age (GA) between infants of same
  birth order in families with and without birth
  defects

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• For the main analyses all birth defects were
  pooled into one group
• In addition the most frequent organ-specific
  malformations were analyzed separately

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Statistics

• T-tests
• Analyses of variance
• Gestational age
• Mothers age (years)
• Mothers education
• Marital status
• Maternal diabetes
• Interpregnancy interval
• Time period

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Results

• Malformed infants had lower mean birth weights
  than control infants of same birth order
• Non-malformed siblings mean birth weights did
  not differ significantly from control infants of
  same birth order (Table I)

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• Gestational age analyses Malformed infants had
  shorter mean GA than control infants
• Non-malformed siblings had mean GA close to that
  of control infants

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• Adjustment for GA reduced the BW difference
  between malformed infants and control infants,
• but had only little impact on the BW differences
  between non-malformed siblings and corresponding
  control infants

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• Adjusting for maternal age, maternal educational
  level, marital status, maternal diabetes, time
  period of first birth and inter-pregnancy
  interval did not change the BW differences
  notably (multiple analyses of variance)

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(No Transcript)
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Organ-specific defects

• Sub-group analyses For most organ-specific
  defects the non-malformed siblings mean BW did
  not differ significantly from that of
  corresponding control infants

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Examples Neural tube defect and Abdominal wall
defect
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Exceptions

• Siblings of infants with multiple malformations,
  and second-born siblings where the first-born
  infant was registered with a cleft lip had
  significantly lower mean BW than control infants
  of same birth order

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Discussion

• BW is strongly correlated within sibships, and
  growth restriction tends to recur in sibships

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• In contrast Reduced BW associated with
  congenital malformations is restricted to the
  pregnancy with the malformed fetus

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• This argues against a theory of growth
  restriction as a primary etiological factor for
  the development of malformations

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• Persisting biological, environmental or
  socioeconomic factors may play different roles
  for the growth restriction associated with
  congenital anomalies and for growth restriction
  not associated with such

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• Exceptions
• Studies have found associations between smoking
  in pregnancy and risk of cleft lip in the
  offspring
• An increased risk of multiple malformations in
  the offspring with decreasing socioeconomic
  status of the family has been reported

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Conclusions

• We conclude that reduced birth weight associated
  with congenital anomalies is specific to the
  affected pregnancy