Long-Term Prognosis of Women with Birth Defects
August 1, 1999
Special Report
Long-Term Prognosis of Women with Birth Defects
By Margaretta Seashore, MD, FAAP
Persons born with birth defects are known to be at high risk for death during the perinatal period and infancy. Much less is known about their later survival, reproduction, and risk of recurrence of birth defects in their offspring. Skjaerven and associates reported on survival and reproductive outcome in a large, national cohort of all women with birth defects identified in a population-based registry of all births in Norway between 1967 and 1997. They compared survival, frequency of childbearing, and frequency of birth defects in offspring in women who had birth defects to outcomes in 451,214 women without birth defects.1 This is an extension of a similar study reported by them in 1994, in which they looked at recurrence of birth defects in children born to women whose first child had a birth defect.2 Their current interesting data are also discussed in an accompanying editorial by Jean Golding.3 They collected information on 459,433 live or stillborn female infants delivered between 1967 and 1982 in Norway. These women were between 15-30 years of age when the data on their survival and childbearing and frequency of birth defects in their offspring were collected. A total of 8192 women with birth defects was identified.
Skjaerven et al present and analyze data about a broad variety of birth defects, including neural tube abnormalities, other CNS defects, musculoskeletal, limb (club foot was considered separately), kidney, genitalia, esophagus, anus, abdominal wall, eye, cardiac, and vascular defects. Also included were cleft lip; cleft palate; defects in skin, hair, and nails; defects in ear, face, and neck; multiple anomalies; and Down’s syndrome. Abnormalities were classified according to ICD-8. The frequency of birth defects in the Norwegian population studied (1.8%) was not significantly different from the approximately 2% incidence of birth defects reported in various surveys around the world.
Survival between the normal and abnormal cohorts of women differed dramatically. The overall survival rate for female infants born during the interval studied was 97.4%. However, the survival rate among infants and children with birth defects was significantly lower. Babies with birth defects were 6.5 times more likely to be stillborn than those without defects. The relative risk of death in the first year of life for subjects with birth defects was 14.8, and in the second year of life, 12.0. Even as far out as the tenth to fourteenth year of life, the relative risk for death was 4.6.
Overall, a total of 62% of the women between the ages of 28 and 30 years had borne children. In every age group, however, there was a lower rate of childbearing among the women with birth defects as compared to those without. The overall ratio of childbearing among surviving affected women compared to those without birth defects was 0.7. Whether a woman with a birth defect gave birth to a child was related to the severity of the birth defect, but even among women with treated birth defects such as club foot, the rate was lower.
Offspring of women affected with a birth defect were more likely themselves to have a birth defect. A total of 1101 women with birth defects gave birth to children, and 3.8% of these children had an identifiable birth defect. This frequency was compared to a 2.4% frequency of birth defects in the offspring of the unaffected women. The offspring of the affected women were much more likely to have the same defect as their mothers than expected by chance. Particular defects that recurred more frequently than others included: cleft palate, cleft lip, club foot, and limb defects. For affected women who gave birth to a child with a dissimilar defect, the relative risk compared to women without birth defects was 1.0, suggesting that a woman with a birth defect is no more likely to have a child with a different birth defect than any other women in the general population. In addition, none of the women with multiple defects gave birth to a child with any defects.
These observations raise a number of interesting questions and provide data to guide counseling of women who are affected with certain birth defects. It has been known since the seminal observations by Carter and Evans in 1982 that certain birth defects recur in multiple generations in families.4 Both individual family studies and population-based studies have corroborated these observations. Certain defects, especially cleft lip and palate, congenital heart defects, and club foot, are classic examples. The multiple generations involved, the similarities among affected relatives, and the decrease in risk to relatives with increasing genetic distance from the proband have all suggested that genetic factors are involved. However, in most situations, the recurrence risks are low and do not reach anything like those of the single gene disorders. The data presented here do not change those conclusions.
The striking new insights described in the study by Skjaerven et al have to do with survival, childbearing rates, and specific recurrence of birth defects. Decreased survival among infants and children with birth defects is not surprising, but the high rates of stillbirth and death in the first two years of life are important for physicians caring for affected women and children to know. Decreased childbearing among women with severe birth defects, especially with intellectual disability and inability to live independently, should not be surprising. It is not clear how much of this decrease might involve social factors and how much may reflect decreased fertility or fetal survival. More data will be needed to sort this out.
Several observations of recurrence risk are of note. Recurrence in offspring was more characteristic of some defects than of others, as has been observed by others. When affected women had a child with a birth defect, it was much more likely to be similar to the one the mother had; indeed, the risk of having a child with other birth defects was not different from the risk in the general population. One of the most helpful observations is that there was no increase in the risk of anomalies in children born to women with multiple anomalies. This parallels the observations made in VACTERYL syndrome association.
There are certain obvious limitations to this kind of study. First, ascertainment of birth defects was confined to the first five days of life. Later identification of conditions, such as congenital heart disease, could change the conclusions about some birth defects. There is no indication that Skjaerven et al went back to examine mothers when a child with a birth defect was identified. Of course, a study using a registry limits that approach. Changes in survival with improved medical care over time could affect their data on survival. Much has changed in the medical and surgical management of congenital malformations since 1967. It is also unclear how the use of prenatal diagnosis may have altered their data in later years. Of course, this study points to a need for further knowledge. We need further understanding of the role of genes in developmental abnormalities. Environmental components may also play a role. It will be useful to identify the reasons for decreased childbearing among these women. More data are needed to determine whether the same outcomes occur for boys and men.
These data have implications for pediatric practice as well as for obstetric practice. For pediatricians, the data point to the importance of anticipatory guidance. The relatively high mortality rate for children (or at least girls) with birth defects in the first few years of life dictates high vigilance on the part of the pediatrician. The more severe the defect, the higher the risk. Optimal medical management will often require a multidisciplinary approach, involving children’s surgeons, clinical geneticists, services for children with special health care needs, and a variety of organ-based specialists. The anticipatory guidance may also need to address the possible reasons for decreased childbearing among these women. To the extent that misinformation or a negative effect on social development is involved, pediatric and genetic counseling can help.
Skjaerven et al have expanded our knowledge of the effect of birth defects on the lives of girls and women. Pediatricians, clinical geneticists, and obstetricians and other primary care providers can use this information to enhance their care of children and families who face the effect of birth defects. (Dr. Seashore is Professor of Pediatrics and Human Genetics at the Yale University School of Medicine.)
References
1. Skjaerven R, et al. A population-based study of survival and childbearing among female subjects with birth defects and the risk of recurrence in their children. N Engl J Med 1999;340:1057-1062.
2. Lie RT, et al. A population-based study of the risk of recurrence of birth defects. N Engl J Med 1994;331:1-4.
3. Golding J. Good news and bad for women with birth defects. N Engl J Med 1999;340:1108.
4. Carter CV, et al. A three generation family study of cleft lip with or without cleft palate. J Med Gen 1982; 19:246-261.
True statements about the long-term survival and reproductive prognosis of women who were born with congenital birth defects include all of the following except:
a. Their mortality during gestation, infancy, and childhood is greater than control women born without birth defects.
b. They are more likely to deliver infants with birth defects similar to their own than expected by chance.
c. Congenital defects that occur in offspring of women with severe defects are also likely to be severe.
d. Their rate of childbearing is the same as that of control women born without birth defects.
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