Long-term survival of children born with congenital anomalies: A systematic review and meta-analysis of population-based studies

Abstract

Background: Following a reduction in global child mortality due to communicable diseases, the relative contribution of congenital anomalies to child mortality is increasing. Although infant survival of children born with congenital anomalies has improved for many anomaly types in recent decades, there is less evidence on survival beyond infancy. We aimed to systematically review, summarise, and quantify the existing population-based data on long-term survival of individuals born with specific major congenital anomalies and examine the factors associated with survival.

Methods and findings: Seven electronic databases (Medline, Embase, Scopus, PsycINFO, CINAHL, ProQuest Natural, and Biological Science Collections), reference lists, and citations of the included articles for studies published 1 January 1995 to 30 April 2020 were searched. Screening for eligibility, data extraction, and quality appraisal were performed in duplicate. We included original population-based studies that reported long-term survival (beyond 1 year of life) of children born with a major congenital anomaly with the follow-up starting from birth that were published in the English language as peer-reviewed papers. Studies on congenital heart defects (CHDs) were excluded because of a recent systematic review of population-based studies of CHD survival. Meta-analysis was performed to pool survival estimates, accounting for trends over time. Of 10,888 identified articles, 55 (n = 367,801 live births) met the inclusion criteria and were summarised narratively, 41 studies (n = 54,676) investigating eight congenital anomaly types (spina bifida [n = 7,422], encephalocele [n = 1,562], oesophageal atresia [n = 6,303], biliary atresia [n = 3,877], diaphragmatic hernia [n = 6,176], gastroschisis [n = 4,845], Down syndrome by presence of CHD [n = 22,317], and trisomy 18 [n = 2,174]) were included in the meta-analysis. These studies covered birth years from 1970 to 2015. Survival for children with spina bifida, oesophageal atresia, biliary atresia, diaphragmatic hernia, gastroschisis, and Down syndrome with an associated CHD has significantly improved over time, with the pooled odds ratios (ORs) of surviving per 10-year increase in birth year being OR = 1.34 (95% confidence interval [95% CI] 1.24-1.46), OR = 1.50 (95% CI 1.38-1.62), OR = 1.62 (95% CI 1.28-2.05), OR = 1.57 (95% CI 1.37-1.81), OR = 1.24 (95% CI 1.02-1.5), and OR = 1.99 (95% CI 1.67-2.37), respectively (p < 0.001 for all, except for gastroschisis [p = 0.029]). There was no observed improvement for children with encephalocele (OR = 0.98, 95% CI 0.95-1.01, p = 0.19) and children with biliary atresia surviving with native liver (OR = 0.96, 95% CI 0.88-1.03, p = 0.26). The presence of additional structural anomalies, low birth weight, and earlier year of birth were the most commonly reported predictors of reduced survival for any congenital anomaly type. The main limitation of the meta-analysis was the small number of studies and the small size of the cohorts, which limited the predictive capabilities of the models resulting in wide confidence intervals.

Conclusions: This systematic review and meta-analysis summarises estimates of long-term survival associated with major congenital anomalies. We report a significant improvement in survival of children with specific congenital anomalies over the last few decades and predict survival estimates up to 20 years of age for those born in 2020. This information is important for the planning and delivery of specialised medical, social, and education services and for counselling affected families. This trial was registered on the PROSPERO database (CRD42017074675).

Fig 1. PRISMA flowchart of searches, screening, and study selection.

PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Fig 2. Survival estimates (with 95% confidence intervals) of children with spina bifida at 1 (a), 5 (b), and 10 (c) years of age over time (10 birth cohorts from 7 studies).

The numbers at survival points indicate the included study, which may appear more than once if survival was reported for more than one birth cohort: 1 –Agha, 2006, Canada; 2 –Borgstedt-Bakke, 2017, western Denmark; 3 –Wong, 2001, Atlanta, USA; 4 –Tennant, 2010, Northern England; 5 –Wang, 2011; USA, 6 –Wang, 2015, USA; 7 –Schneuer, 2019, New South Wales, Australia.

Fig 3. Survival estimates (with 95% confidence intervals) of children with oesophageal atresia at 1 (a) and 5 (b) years of age over time (7 studies).

The numbers at survival points indicate the included study: 1 –Cassina, 2016, Northeast Italy; 2 –Garne, 2002, Funen, Denmark; 3 –Oddsberg, 2012, Sweden; 4 –Tennant, 2010, Northern England; 5 –Wang, 2011 USA; 6 –Wang, 2015, USA; 7 –Schneuer, 2019, New South Wales, Australia.

Fig 4. Survival estimates (with 95% confidence intervals) of children with biliary atresia at 5 (a) and 10 (b) years of age over time (11 birth cohorts from 9 studies).

The numbers at survival points indicate the included study which may appear more than once if survival was reported for more than one birth cohort: 1 –McKiernan, 2000, UK and Ireland; 3 –Nio, 2003, Japan; 6 –Tennant, 2010, Northern England; 8 –Wildhaber, 2008, Switzerland; 9 –Davenport, 2011, England and Wales, 10 –Chardot, 2013, France; 11 –Pakarinen, 2018, Nordic countries; 13 –Grizelj, 2010, Croatia; 15 –Tu, 2015, South Australia.

Fig 5. Survival estimates (with 95% confidence intervals) of children with congenital diaphragmatic hernia at 1 (a) and 5 (b) years of age over time (5 studies).

The numbers at survival points indicate the included study: 2 –Garne, 2002, Denmark; 6 –Tennant, 2010, Northern England; 7 –Wang, 2011, USA; 8 –Wang, 2015, USA; 9 –Schneuer, 2019, New South Wales, Australia.

Fig 6. Survival estimates (with 95% confidence intervals) of children with gastroschisis at 1 (a) and 5 (b) years of age over time (5 studies).

The numbers at survival points indicate the included study: 1—Risby, 2017, southern Denmark; 2—Schneuer, 2019, New South Wales, Australia; 3—Tennant, 2010, Northern England; 4—Wang, 2011, USA; 5—Wang, 2015, USA.

Fig 7. Survival estimates (with 95% confidence intervals) of children with Down syndrome associated with congenital heart defect at 1 (a), 5 (b), and 10 (c) years of age over time (11 birth cohorts from 10 studies).

The numbers at survival points indicate the included study, which may appear more than once if survival was reported for more than one birth cohort: 1 –Glasson, 2016, Western Australia; 2 –Hayes, 1997, Ireland; 3 –Kucik, 2013, USA; 4 –Leonard, 2000, Western Australia; 5 –Rankin, 2012, Northern England; 6 –Rasmussen, 2006, Atlanta, USA; 10 –Brodwall, 2018, Norway; 11 –Frid, 1999, northern Sweden; 12 –Halliday, 2009, Victoria, Australia, 13 –Schneuer, 2019, New South Wales, Australia.

Fig 8. Survival estimates (with 95% confidence intervals) of children with Down syndrome without congenital heart defect at 1 (a), 5 (b), and 10 (c) years of age over time (11 birth cohorts from 10 studies).

The numbers at survival points indicate the included study, which may appear more than once if survival was reported for more than one birth cohort: 1 –Glasson, 2016, Western Australia; 2 –Hayes, 1997, Ireland; 3 –Kucik, 2013, USA; 4 –Leonard, 2000, Western Australia; 5 –Rankin, 2012, Northern England; 6 –Rasmussen, 2006, Atlanta, USA; 10 –Brodwall, 2018, Norway; 11 –Frid, 1999, northern Sweden; 12 –Halliday, 2009, Victoria, Australia, 13 –Schneuer, 2019, New South Wales, Australia.