Congenital Malformations in Infants Born to Young Mothers

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Jane A. Evans and Amanda Fortier
Department of Biochemistry and Medical Genetics
University of Manitoba, Winnipeg, Manitoba

Table of Contents

• Introduction
• Methods
• Results
• Discussion
• Acknowledgments
• References

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Introduction

Unlike older women, whose increased risk of having infants with chromosomal anomalies has long been recognized, young mothers have rarely been considered as being particularly vulnerable to having children with congenital malformations. However, what data do exist suggest that the distribution of maternal age specific prevalence rates for many birth defects is J-shaped rather than exponential or linear ^1,2.

Certain defects have consistently shown what Lubinsky ³ referred to as a “decreased maternal age effect” with young women, usually defined as less than 20 years of age, having higher rates compared to a control group, usually women between 25 and 29 years. These disorders include gastroschisis ^{3-6 , 7}; patent ductus arteriosus and hypertrophic pyloric stenosis ⁸ ; spina bifida ⁴ , hydranencephaly and septo-optic dysplasia ^9,10; optic nerve hypoplasia ¹¹; anencephaly, cleft lip and polydactyly ², and schizencephaly ¹².

Although the reasons for a decreased maternal age effect are not clear, several hypotheses have been presented. Elster ¹³ suggested that competition for nutrients between the still growing mother and the developing fetus may adversely effect pregnancy outcome. Torfs et al. 5 considered that incomplete reproductive maturity could explain the increased risk of congenital malformations in young mothers. Lubinsky³ took a different approach, suggesting that there may be a protective effect of later motherhood, while Croen and Shaw ¹ considered that younger mothers might be more likely to carry a malformed fetus to livebirth.

Many of the conditions that fall into the decreased maternal age effect category can be considered vascular disruption defects. These are defined as structural anomalies that result from damage to or interruption of normal vascular development ^3,14,15. There are many mechanisms by which vascular disruptions occur. These can affect the uterine-placental unit e.g. acute or chronic decrease in uterine blood flow or abnormal uterine anatomy; the fetal-placental unit such as placental insufficiency, umbilical cord compression or anastamoses in twin placentas; or the vasculature within the fetus itself from occlusion by emboli, disruption of newly formed vessels or failure of certain vessels to involute at the appropriate time in development.

Environmental factors that have been implicated in causing vascular defects include cocaine, nicotine and other vasoconstrictive drugs ^16,17. Hyperthermia and generalized infection ¹⁴, alcohol, caffeine, and salicylates and other analgesics may also be risk factors ¹⁸. Some of these risk factors are potentially more prevalent among young mothers who may also present later for prenatal care ¹³ and thus be less likely to be eligible for screening programs such as maternal serum screening⁴ thereby making detection of fetal anomalies and termination of pregnancy less likely. Population studies have shown that low levels of maternal education, low income and unwed marital status, all of which are more prevalent among adolescent mothers, also increase the risk of abnormal pregnancy outcomes ⁵.

In order to evaluate the effect of young maternal age on congenital malformation rates in our population, we carried out an investigation using data from the Manitoba Maternal Serum Screening Program. The data reported here relate to a subset of liveborn infants with congenital anomalies.

Methods

Liveborn infants with congenital anomalies, coded by ICD-9 codes 740.0 to 759.9, were identified among the outcomes of 61,417 pregnancies screened by maternal serum screening in Manitoba between 22 January 1990 and 17 September 1998. Duplicate records and erroneous codes were removed. The gestational ages of all infants with codes for patent ductus arteriosus or cryptorchidism were ascertained and records of infants less than 37 weeks of gestation at birth were excluded from further analysis. The malformed infants were subdivided into groups based on the first three digits of the ICD-9 code and the distribution of maternal ages compared across eight five-year maternal age categories. After cases with chromosomal defects were removed, the records were ordered by their screening identification number, which is assigned sequentially at the time of screening. From this database, each woman who was less than 20 years of age at the estimated date of delivery (EDD) was identified as a case. For each case, the next woman in the database whose age at EDD was greater than 25 but less than 29 years of age was selected as a control. Where there were sufficient numbers of cases to assess specific birth defects using a four or five digit code, the numbers of affected infants were compared between the groups using Chi-square analysis. The numbers of multiple anomalies cases and those with “vascular” defects were also compared.

Results

A total of 3483 infants fitting our criteria for congenital malformations were identified representing 5.67% of the total population. Among these, 467 (13.4%) had multiple anomalies. In the analysis of three-digit codes, 740 (anencephaly and related disorders) and 741 (spina bifida) had fewer than 20 liveborn cases due to prenatal diagnosis and pregnancy termination or fetal loss, thus their distributions were not examined further. With respect to the other 18 three digit codes, some such as 743: congenital anomalies of the eyes and 749: cleft lip and palate showed a normal distribution of maternal age; others such as 742: other congenital anomalies of the nervous system, 745: bulbus cordis anomalies and defects of cardiac septal closure, and 758: chromosomal anomalies, were skewed towards older mothers; while still others including 751: other anomalies of the digestive system, 756: other congenital musculoskeletal anomalies and 759: other and unspecified anomalies were skewed towards younger mothers.

In the case control study, 106 four and five digit codes were subjected to Chi-square analysis. Five showed significant differences at the p<0.01 level compared to the one that would be expected by chance. In only one, 744.1: accessory auricle (p<0.005) was the defect more common in 25-28 year olds. All the others: 745.2: Tetralogy of Fallot (p<0.0005), 753.15: renal dysplasia (p<0.005), 753.19: other specific renal disease (p<0.005) and 757.3: other anomalies of the skin (p<0.01), were more common in the infants born to women under 20 years of age. Cases with vascular type defects in general or multiple congenital anomalies showed no differences between the two age groups.

Discussion

This study of liveborn infants did not show that those born to women under 20 years of age had a higher rate of congenital anomalies overall. However, certain defects were more common in this age group. The increased frequency of renal anomalies was interesting as some of these may be vascular in nature. A follow-up study of these defects ¹⁹ confirmed the decreased maternal age effect.

Although we could not evaluate ethnicity in the population under study, the increased prevalence of integumentary anomalies in our younger mothers may be related to the higher teenage pregnancy rate among Aboriginal populations, who have a high incidence of Mongolian spots ²⁰. Mongolian spots are a normal variant in Aboriginal infants, but are listed under code 757.38 in ICD9 and thus may have erroneously been coded as malformations. To determine if this is a factor, we would need to carry out a chart review of the cases to determine the precise nature of the skin defects.

Tetralogy of Fallot has not previously been reported to be associated with decreased maternal age and this finding would be worth investigating further in a larger population.

With the exception of non-osseous syndactyly of the fingers (755.11 p<0.05), no recognized vascular defects were more common in the young mothers. This may in part be due to the fact that the study concentrated on liveborn infants. Certainly, cases of gastroschisis were identified and were seen in mothers less than 20 years of age. Further analysis of IDC-9 655 codes and inclusion of terminated pregnancies would allow a more complete evaluation, while a larger sample and more detailed data would allow for correction of anomaly rates by infant sex, ethnicity and parity.

Although young pregnant mothers can be reassured that their overall risk of having a child with congenital anomalies is still relatively low, their fetuses may be predisposed to certain defects. As for women at any age, preconceptional and prenatal counseling should stress avoidance of factors such as smoking, alcohol consumption, hyperthermia and illicit drug use that could increase their risk, as well as the importance of good nutrition and multivitamin supplementation.

Although women could potentially reduce their risk of certain fetal malformations by delaying childbirth to their mid twenties, many pregnancies, especially those in teenagers, are unplanned. If adolescents do become pregnant, they should be encouraged to seek prenatal care as soon as possible and offered prenatal screening using maternal serum markers and ultrasonography with special regard for vascular type defects.

Acknowledgments

We would like to thank Dr. Bernie Chodirker and Karen MacDonald of the Manitoba Maternal Serum Screening Program for help in retrieving the necessary data files. Amanda Fortier carried out these analyses as part of her fourth year honours project in human genetics at the University of Manitoba under the supervision of Jane Evans. Amanda is currently a PhD student at McGill University.

REFERENCES

1. Croen LA, Shaw GM. Young maternal age and congenital malformations: a population-based study. Am J Public Health 85(5):710, 1995.
2. Reefhuis J, Honein MA. Maternal age and non-chromosomal birth defects, Atlanta--1968-2000: teenager or thirty-something, who is at risk? Birth Defects Res A Clin Mol Teratol 70(9):572, 2004.
3. Lubinsky MS. Association of prenatal vascular disruptions with decreased maternal age. Am J Med Genet 69(3):237, 1997.
4. Haddow JE, Palomaki GE, Holman MS. Young maternal age and smoking during pregnancy as risk factors for gastroschisis. Teratology 47(3):225, 1993.
5. Torfs CP, Velie EM, Oechsli FW, Bateson TF, Curry CJ. A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors. Teratology 50(1):44, 1994.
6. Calzolari E, Volpato S, Bianchi F, Cianciulli D, Tenconi R, Clementi M et al. Omphalocele and gastroschisis: a collaborative study of five Italian congenital malformation registries. Teratology 47(1):47, 1993.
7. Nichols CR, Dickinson JE, Pemberton PJ. Rising incidence of gastroschisis in teenage pregnancies. J Matern Fetal Med 6(4):225, 1997.
8. Baird PA, Sadovnick AD, Yee IM. Maternal age and birth defects: a population study. Lancet 337(8740):527, 1991.
9. Lubinsky MS, Adkins W, Kaveggia EG. Decreased maternal age with hydranencephaly. Am J Med Genet 69(3):232, 1997.
10. Lubinsky MS. Hypothesis: septo-optic dysplasia is a vascular disruption sequence. Am J Med Genet 69(3):235, 1997.
11. Tornqvist K, Ericsson A, Kallen B. Optic nerve hypoplasia: Risk factors and epidemiology. Acta Ophthalmol Scand 80(3):300, 2002.
12. Curry CJ, Lammer EJ, Nelson V, Shaw GM. Schizencephaly: heterogeneous etiologies in a population of 4 million California births. Am J Med Genet A 137(2):181, 2005.
13. Elster AB. The effect of maternal age, parity, and prenatal care on perinatal outcome in adolescent mothers. Am J Obstet Gynecol 149(8):845, 1984.
14. Bavinck JN, Weaver DD. Subclavian artery supply disruption sequence: hypothesis of a vascular etiology for Poland, Klippel-Feil, and Mobius anomalies. Am J Med Genet 23(4):903, 1986.
15. Van Allen MI. Structural anomalies resulting from vascular disruption. Pediatr Clin North Am 39(2):255, 1992.
16. Bingol N, Fuchs M, Diaz V, Stone RK, Gromisch DS. Teratogenicity of cocaine in humans. J Pediatr 110(1):93, 1987.
17. Werler MM, Sheehan JE, Mitchell AA. Association of vasoconstrictive exposures with risks of gastroschisis and small intestinal atresia. Epidemiology 14(3):349, 2003.
18. Werler MM, Mitchell AA, Shapiro S. First trimester maternal medication use in relation to gastroschisis. Teratology 45(4):361, 1992.
19. Evans JA, Bisson D, Fortier A. Is there a decreased maternal age effect for renal a/dysplasia? Proc Greenwood Genet Cen 21:108-109, 2002.
20. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders, 2006.

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