Congenital malformations and birth weight by sammyc2007

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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
 Why is it fascinating to
   study families?
• Familiesconstitute small
”populations” with shared genetic
and environmental features
•Dependencies between family
members have implications for
risk assessment (for instance of
adverse pregnancy outcome)
  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
   Background for this
         study:

• There is a large and
  significant correlation between
  siblings’ birth weights
• Low birth weight tends to
  recur in sibships
• In general, infants with
  congenital malformations
  have lower mean birth
  weight than infants without
  malformations
• 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
          Objective:
• To study birth weight of
  malformed infants’ siblings
• ..and compare with birth
  weight of infants in families
  without any registered
  malformations
 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
    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
• 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
 Table I            First       Second
                    birth order birth order
Family group Number BW (SD) BW (SD)

No BD        525,758 3426 (581) 3574 (578)

BD 1st sib   13,519   3242 (811) 3569 (596)

BD 2nd sib   11,519   3410 (597) 3365 (846)

BD both sibs 682      3252 (779) 3328 (890)
  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
 Analyses:

• We compared mean birth
  weight (BW) and gestational
  age (GA) between infants of
  same birth order in families
  with and without birth defects
• For the main analyses all
  birth defects were pooled
  into one group
• In addition: the most frequent
  organ-specific malformations
  were analyzed separately
           Statistics:
• T-tests
• Analyses of variance
  – Gestational age
  – Mother’s age (years)
  – Mother’s education
  – Marital status
  – Maternal diabetes
  – Interpregnancy interval
  – Time period
             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)
• Gestational age analyses:
  Malformed infants had
  shorter mean GA than
  control infants
• Non-malformed siblings had
  mean GA close to that of
  control infants
• 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
• 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)
  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
  Examples: Neural tube defect
   and Abdominal wall defect
              st               nd
               1 sib          2 sib
Family:   dBW 95%CI dBW 95%CI
Ref-gr    3541            3690
NTD-1     - 474 -524;-424 - 5     -54; 45
NTD-2      - 15   -70; 40 - 431 -488;-374
AWD-1     -135 -197;-74     49   -11; 108
AWD-2       19    -42; 81  - 84 -146; -21
          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
         Discussion:

• BW is strongly correlated
  within sibships, and growth
  restriction tends to recur in
  sibships
• In contrast: Reduced BW
  associated with congenital
  malformations is restricted to
  the pregnancy with the
  malformed fetus
• This argues against a theory
  of growth restriction as a
  primary etiological factor for
  the development of
  malformations
• 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
• 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
       Conclusions:
• We conclude that reduced
  birth weight associated with
  congenital anomalies is
  specific to the affected
  pregnancy

								
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