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Original article
The burden of selected congenital anomalies amenable to surgery in low and middle-income regions: cleft lip and palate, congenital heart anomalies and neural tube defects
  1. Hideki Higashi1,2,
  2. Jan J Barendregt2,
  3. Nicholas J Kassebaum1,3,
  4. Thomas G Weiser4,
  5. Stephen W Bickler5,
  6. Theo Vos1,2
  1. 1Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, USA
  2. 2School of Population Health, University of Queensland, Brisbane, Queensland, Australia
  3. 3Division of Anesthesiology & Pain Medicine, Seattle Children's Hospital, Seattle, Washington, USA
  4. 4Department of Surgery, School of Medicine, Stanford University, Stanford, California, USA
  5. 5Department of Surgery, School of Medicine, University of California, San Diego, California, USA
  1. Correspondence to Dr Hideki Higashi, Institute for Health Metrics and Evaluation, University of Washington, 2301 Fifth Ave, Suite 600, Seattle, WA 98121, USA; h.higashi{at}uqconnect.edu.au

Abstract

Objective To quantify the burden of selected congenital anomalies in low and middle-income countries (LMICs) that could be reduced should surgical programmes cover the entire population with access to quality care.

Design Burden of disease and epidemiological modelling.

Setting LMICs from all global regions.

Population All prevalent cases of selected congenital anomalies at birth in 2010.

Main outcome measures Disability-adjusted life years (DALYs).

Interventions and methods Surgical programmes for three congenital conditions were analysed: clefts (lip and palate); congenital heart anomalies; and neural tube defects. Data from the Global Burden of Disease 2010 Study were used to estimate the combination of fatal burden that could be addressed by surgical care and the additional long-term non-fatal burden associated with increased survival.

Results Of the estimated 21.6 million DALYs caused by these three conditions in LMICs, 12.4 million DALYs (57%) are potentially addressable by surgical care among the population born with such conditions. Neural tube defects have the largest potential with 76% of burden amenable by surgery, followed by clefts (59%) and congenital heart anomalies (49%). Sub-Saharan Africa and South Asia have the greatest proportion of surgically addressable burden for clefts (68%), North Africa and Middle East for congenital heart anomalies (73%), and South Asia for neural tube defects (81%).

Conclusions There is an important and neglected role surgical programmes can play in reducing the burden of congenital anomalies in LMICs.

  • Congenital Abnorm
  • Epidemiology
  • Paediatric Surgery

https://doi.org/10.1136/archdischild-2014-306175

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    What is already known on this topic?

    • From the Global Burden of Disease 2010 Study, congenital anomalies account for 302 000 infant deaths, 96% of which occur in low and middle-income countries.

    • Some congenital anomalies, including cleft lip and palate, congenital heart anomalies and neural tube defects, can be treated by specialised surgical procedures.

    • Such surgical services require specialised skills and infrastructure that they are often provided as vertical programmes in low and middle-income countries.

    What this study adds?

    • Disease burden associated with cleft lip and palate, congenital heart anomalies and neural tube defects in low and middle-income regions could be halved by scaling up surgical care.

    • Vertical surgical programmes, including training, deserve due attention so as not to leave an important cause of premature infant death and long-term disability unaddressed.

    Introduction

    Congenital anomalies constitute a major cause of infant mortality, and patients that survive often live with disabilities that continue into adulthood. Approximately 3% of live births are associated with some kind of birth defect. Findings from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2010 suggest that 302 000 infants die from causes attributable to congenital anomalies (6% of all infant deaths), 96% of which occur in low and middle-income countries (LMICs).1

    Certain congenital anomalies can be treated by specialised operations, in particular clefts, neural tube defects and congenital heart anomalies. While some tertiary referral hospitals in LMICs may provide surgical care for these conditions,2 the advanced skills required for the procedure often hinder its incorporation into the general healthcare system. Therefore these conditions have often been managed by establishing vertical programmes in LMICs, frequently supported by international funding and surgical missions.3–5 The Disease Control Priorities Project6 identified surgery as an essential component of public health, where congenital anomalies accounted for 9% of burden estimated to be amenable to surgical care.7

    This work has been conducted as part of a systematic estimate of surgical burden for the updated Disease Control Priorities Project. We aim to quantify the degree by which the burden of congenital anomalies could be reduced among children born with the conditions in LMICs in what we would consider a ‘hypothetical’ state where the entire population has access to safe, reliable, efficacious and high quality surgical care.

    Methods

    Selection of conditions for analysis

    We examined three surgical conditions: clefts (lip and palate); congenital heart anomalies; and neural tube defects. These conditions were selected from the GBD 2010 cause list because they constitute a major burden of congenital anomalies (58% of burden of congenital anomalies in GBD 2010; see table 1 for estimates),1 because a reasonable amount of data and knowledge on epidemiology are available, and because there are clearly corresponding and established surgical programmes. While there are other congenital conditions that are correctable by surgery, most of them fall within the heterogeneous category of ‘other congenital conditions' in GBD 2010, and hence a reasonable analysis of the proportion amenable to surgery could not be made. Disease-specific background information for the selected conditions is provided in the online appendix section 1.

    View this table:
    Table 1

    Burden of selected congenital anomalies in low and middle-income countries, 2010

    Approach and analysis

    The base population for the analysis was all prevalent cases of each congenital anomaly at birth in 2010. Disability-adjusted life year (DALY) was used as the metric of burden that combines fatal burden and non-fatal burden of a health condition into a single index: years of life lost; and years lived with disability (YLDs). The burden of congenital anomalies reported in GBD 2010 was split into burden that is amenable to surgery and burden that is not. We first estimated the DALYs that would remain if surgical coverage had been scaled up to a hypothetical state of comprehensive, high quality surgical coverage, and defined this as the burden not amenable to surgery. We then subtracted it from the burden reported in the GBD 2010 to derive the burden amenable to surgery.

    We obtained data from the GBD 2010.1 Key parameters included: population, standard life expectancy, cause-specific mortality, prevalence and disability weight.8–10 The GBD 2010 employed a Bayesian meta-regression programme, DisMod-MR, which is built on an age-integrating mixed-effects negative-binomial model for all epidemiological parameters.9 The model incorporates covariates that predict variation in true rates between regions and that predict systematic variation across different types and sources of data (measurement bias) to produce and extrapolate an internally consistent set of epidemiological parameters for all regions that are specific to age, sex and year. The GBD 2010 grouped the countries into 21 epidemiological regions and seven super-regions (of which six regions group LMICs). Our analysis was conducted at the super-region level.

    We first estimated the non-fatal burden of each condition for the hypothetical circumstance of surgical coverage in LMIC super-regions (see online appendix subsection 2.1 for details). We assumed that the difference in prevalence between a particular age-group and the next in the high-income super region reflects the excess mortality of congenital anomalies in case of the hypothetical surgical coverage. Such excess mortality includes deaths attributed to anomalies as well as deaths coded otherwise that contribute to higher all-cause mortality among those with congenital anomalies compared with those without. Beginning with the birth prevalence in each region, we applied this assumption to age 1 year and above to follow the age-specific prevalence. The resulting prevalence for each sex and age was then multiplied by the disability weights of each to derive the YLDs condition (see online appendix subsection 2.1 for the disability weights used).

    Next, we estimated the fatal burden attributable to congenital anomalies under the hypothetical situation (see online appendix subsection 2.2 for details). We assumed that the lowest mortality rates of congenital anomalies (ie, number of deaths attributable to each congenital condition per prevalent case) among the 21 epidemiological regions for each age and sex reflect 100% surgical coverage, and hence the difference of mortality rates between each region and the lowest as reflecting the gap of surgical coverage. The majority of lowest mortality rates were from high-income regions (ie, Asia Pacific High Income, Australasia, Europe Western and North America High Income). By applying the lowest mortality rates to the prevalence of a hypothetical state as estimated above, we calculated the number of deaths attributable to each congenital condition for the hypothetical situation. We then multiplied the number of deaths by the age-specific standard life expectancy used in GBD 2010.8 ,11 Finally, we summed up non-fatal burden and fatal burden to derive the DALYs for the hypothetical state.

    For clefts, we conducted an extra analysis. The years of life lost of clefts in GBD 2010 only included those deaths coded as clefts being the underlying cause under the age of 5 years. This is potentially an underestimation of the true burden at the age of 5 years and above. If we compare the two epidemiological models from DisMod-MR that were used to estimate the YLDs of clefts (one for surgically repaired cases and another one for non-repaired cases),9 we see a sharp decline in prevalence as the non-repaired cases age, while that among repaired cases remains fairly steady throughout the life course (see online appendix section 3). This implies that the excess mortality due to any cause among the non-repaired clefts is far more prominent than those that had undergone repair, suggesting extra opportunities for reducing the burden of clefts through surgical repairs. We conducted a separate analysis using the set of parameters produced by the DisMod-MR models reflecting the excess mortality due to any cause rather than merely accounting for deaths that are attributed to clefts (see online appendix section 4 for details).

    Results

    Of the three congenital anomalies studied, deaths could be reduced by 67% and the disease burden by 57% in the population born with those conditions in LMICs by scaling up surgical programmes and providing comprehensive, efficacious, high quality interventions (see table 2). Deaths coded as being attributable to clefts can be reduced by appropriate surgery to virtually zero. Deaths from congenital heart anomalies appear more difficult to prevent (58%) while deaths from neural tube defects can be reduced by 90%.

    View this table:
    Table 2

    Burden of congenital anomalies amenable to surgery in low and middle-income regions

    Sub-Saharan Africa and South Asia have the largest proportion of burden of clefts amenable to surgery (68%), and East Europe and Central Asia and North Africa and Middle East the least (38–40%). While some of the regions have similarly high proportions of burden of neural tube defects amenable to surgery (about 80%), North Africa and Middle East, and perhaps East Asia Pacific, have a relatively low proportion (44–60%). In comparison to congenital heart anomalies, the proportion of DALYs of neural tube defects amenable to surgery is smaller than the deaths avoidable by surgery (76% vs. 90%, respectively). The results of congenital heart anomalies are rather counterintuitive that sub-Saharan Africa and South Asia have the smallest proportion of burden amenable to surgery (3% and 29%, respectively). The results from the extra analysis we conducted for clefts where we have taken into account the excess mortality due to any cause experienced by non-repaired cases are provided in table 3. The results demonstrate a 15-fold difference in the burden amenable to surgery (5.1 million as opposed to 0.33 million). Figures 1⇓–3 visualise the results for each condition.

    View this table:
    Table 3

    Burden of clefts amenable to surgery in low and middle-income regions (with all-cause excess mortality)

    Figure 1
    Figure 1

    Surgical burden of clefts in six LMIC super regions ((A) coded deaths only; (B) including all-cause excess mortality). DALY, disability-adjusted life year; LMICs, low and middle-income countries.

    Figure 2
    Figure 2

    Surgical burden of congenital heart anomalies in six LMIC super regions. DALY, disability-adjusted life year. LMICs, low and middle-income countries.

    Figure 3
    Figure 3

    Surgical burden of neural tube defects in six LMIC super regions. DALY, disability-adjusted life year. LMICs, low and middle-income countries.

    Discussion

    The burden of the three conditions amenable to surgery accounts for 33.5% of burden of all congenital anomalies in LMICs (37 million DALYS). By comparing the 12.4 million DALYs that is amenable to surgery with other global health challenges, the burden is equivalent to 11% of burden of ischaemic heart disease in LMICs (109 million DALYs in 2010) or 15% of that of HIV/AIDS (80.6 million DALYs in 2010).1 As is evident from the extra analysis conducted for clefts, the burden amenable to surgery could be even greater if excess mortality due to any cause that may be associated with neural tube defects and congenital heart anomalies were also taken into account.

    Generally, the higher proportion of burden amenable to surgery implies that a relatively small portion of burden had been avoided prior to 2010. The large proportion of burden of clefts amenable to surgery in sub-Saharan Africa and South Asia therefore reflects the low coverage of surgical care in 2010. The international charity Smile Train has been the largest provider of cleft repairs in China since 1999, contributing to the high surgical coverage in East Asia Pacific (285 000 repairs in China to date).5 Recently the same charity has been accelerating its operations in India (335 000 repairs to date), which is likely reducing the burden in South Asia since 2010. Given that the extra analysis of clefts revealed a large number of deaths that may be associated with, yet not attributed to, clefts, surgical repair of clefts has the potential to further reduce the burden that has been attributed to other conditions.

    Surgical repair for congenital anomalies have often been accomplished through vertical programmes such as specialised clinics and medical missions. As the global health community looks beyond 2015 and the close of the Millennium Development Goals, the global health agenda is shifting towards a more systemic approach.12 Accordingly such surgical programmes should be incorporated in the general healthcare delivery framework through training and enhanced local infrastructure. Specialised surgical training programmes have been provided in Africa, Latin America, Asia and East and Central Europe, frequently by foreign charities that participate in clinical care and capacity development. However, the complex nature of these operations would likely be a non-trivial endeavour, at least in the short run, and vertical programmes could continue to fill in the gap until such time when local providers become capable of performing such operations, and providing training, on their own.

    This study is the most rigorous, data-driven estimation of burden of congenital anomalies amenable to surgery to date. As with any modelling and estimation exercise, assumptions were required that should be noted. The mortality data used in this study reflect those deaths where each of the three anomalies was coded as the underlying cause. There may be cases where deaths immediately following births due to congenital anomalies were coded elsewhere, such as ‘stillbirth’, causing underestimation of the burden. The counterintuitive results of the low proportion of burden of congenital heart anomalies amenable to surgery in sub-Saharan Africa and South Asia are likely due to coding practices. When comparing the infant mortality rates due to congenital heart anomalies between regions, sub-Saharan Africa and South Asia had substantially lower rates than other regions (9% and 29% as compared with an average of 68% in other LMIC regions). Given the sharp decline in prevalence between infants and the 1–4 years age group, it is likely that a significant proportion of deaths were coded elsewhere. While verbal autopsy is frequently the source of data in determining the cause of death in these regions, congenital heart anomalies are not likely to be identified properly as the underlying cause. Should this be the case, the burden of congenital heart anomalies amenable to surgery estimated for these two regions is potentially underestimated.

    We assumed that the lowest fatality estimates from the 21 epidemiological regions reflect the ideal case of full surgical coverage. A situation of full surgical coverage assumed here allows for timely access to surgical care, physically and financially, with sufficient quality when operation is warranted. Such a situation would potentially entail a mix of infrastructure, transport, appropriate skills and financing mechanisms. While most of the estimates were from high-income regions, it is not clear if those figures are applicable to other settings. Even if vertical programmes with foreign support, such as surgical missions, are able to reach the entire population, health-seeking behaviour may vary between regions and cultures. Some cases may need follow-up support leading to different long-term health outcomes, which depends on the total health system rather than the surgical care alone. These issues may have resulted in an overestimation of burden amenable to surgery. Another limitation is the absence of uncertainty intervals in the results. While the GBD 2010 study reported the uncertainty intervals of the estimated disease burden, only point estimates are reported in our analysis. The main sources of uncertainty in our study are the assumptions we had to make. Doing uncertainty analysis based on the uncertainty interval (credible or Bayesian CI) in the GBD 2010 estimates provides a false sense of precision because it does not include this main source of uncertainty.

    Finally, this analysis was conducted at the regional level due to the nature of GBD 2010, while results at the country level would have been more useful for policy making. The occurrence of neural tube defects is known to be preventable by appropriate folic acid intake in early pregnancy, and so the potential of surgical operations in reducing disease burden should not be interpreted as discouraging such critical interventions. In the global context, interventions for child health in LMICs have been largely targeting infectious diseases and nutritional conditions through vaccination, nutrition supplementation, water and sanitation, etc. While our analysis alludes to the magnitude of impact surgical operations could contribute to global health, we did not investigate the relative efficiency of surgical care in comparison to those other priority agenda. Therefore we are not able to suggest whether limited resources should be reallocated from those traditional child health interventions to paediatric surgery with a view of maximising health outcomes. While a number of studies have examined the cost-effectiveness of different surgical procedures in LMICs,13 future studies investigating the cost-effectiveness of these particular procedures would complement our study.

    Conclusions

    There are substantial opportunities for specialised surgical interventions to reduce the burden of congenital anomalies in LMICs. Such programmes may not become immediately available through general healthcare delivery systems due to the associated complexity, and hence may be overlooked in planning essential health services packages. Governments of LMICs and donor communities should pay due attention to these essential surgical programmes so as not to leave an important cause of premature infant death and long-term disability unaddressed.

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    Footnotes

    • Contributors HH participated in conceptualising and designing of the study, performed primary analyses, and drafted the initial manuscript. JJB and TV participated in conceptualising and designing of the study, provided analytical expertise, and critically reviewed the manuscript. NJK, TGW and SWB participated in conceptualising and designing of the study, provided technical expertise of surgery, and critically reviewed the manuscript. All authors approved the final manuscript as submitted.

    • Funding This research was supported by the Bill and Melinda Gates Foundation under the Disease Control Priorities Network Project.

    • Competing interests None.

    • Provenance and peer review Not commissioned; externally peer reviewed.