Integrated Newborn Screening in Nigeria: The Way Forward, A Workshop Report

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript addresses a highly relevant public health topic, particularly for low- and middle-income countries, and is timely given the increasing global focus on integrated newborn screening. Overall, the article is of interest; however, several scientific and methodological aspects require clarification or improvement to strengthen the manuscript.

Abstract

• The abstract is informative but should explicitly state that the manuscript is a workshop report and expert consensus document, rather than an original research study.
• In addition, the abstract presents conclusions and strategic outcomes without explaining how consensus was achieved. A brief mention of the methodology used to synthesize expert input (guided discussions, consensus agreement) would improve transparency.

Introduction

• The introduction provides a solid overview of the importance of newborn screening and appropriately contextualizes the Nigerian situation within the global landscape. However, statements such as “over 50 conditions are routinely screened globally” should be qualified, as the number of screened conditions varies widely depending on country and resource level. The authors are encouraged to provide more specific data, such as examples illustrating the wide variety of conditions that may be included in newborn screening panels, and to mention conditions that are screened in some countries or regions but not in others, in order to better convey the heterogeneity of global newborn screening practices.
• It is recommended to conclude the introduction with a clear statement of the manuscript’s objective, explicitly indicating that the aim is to report the outcomes of a national workshop and propose a strategic framework for newborn screening implementation in Nigeria.

Organization: The description of participating institutions and stakeholders is comprehensive and informative. Nevertheless, the manuscript lacks a basic description of the workshop methodology. It would be important to clarify: approximately how many participants attended, how the sessions were structured (e.g., plenary sessions, working groups), how decisions and final recommendations were reached. Including this information would enhance the credibility and reproducibility of the consensus process.

Summary of presentations

Laboratory perspectives

• Advanced technologies such as LC-MS/MS and genomic sequencing are discussed. In addition to what Professor Anetor has said, while scientifically accurate, it should be more clearly stated that current newborn screening programmes worldwide are still primarily based on conventional biochemical screening, including mass spectrometry–based approaches among other techniques, and that genomic screening is an emerging tool that is not yet implemented in the majority of newborn screening programmes globally. Genomic approaches should therefore be clearly presented as a future or complementary strategy, rather than as a requirement for initial implementation. It would be appropriate to support these claims with direct references.

Clinical perspectives

• The importance of early screening and treatment for congenital hypothyroidism is well presented. However, when specific screening windows and treatment timelines are mentioned, it would be appropriate to support these claims with direct references.

World Health Organization

• Dr Ayesha De-Costa noted that 90% of children with serious congenital anomalies are born in LMICs and advocated for integrating newborn screening into routine health systems. It is necessary to indicate the original reference.

Key Discussion Points

• It would be important to include basic demographic data on births in Nigeria. Specifically, the authors should indicate approximately how many births occur annually, and whether this number has increased in recent years, as this information is essential to contextualise the scale, feasibility, and potential impact of a national newborn screening programme.

Prioritisation of target conditions

• It would strengthen the manuscript to explicitly explain how sickle cell disease and congenital hypothyroidism fulfil the Wilson and Jungner screening criteria. What incidence should a disease have in order to be considered for newborn screening?
• Why have other diseases, such as certain amino acid disorders or beta-oxidation defects, been ruled out? Is their future implementation possible? Perhaps it would be good to indicate this in the text.
• Be careful with abbreviations. For example, congenital hypothyroidism has been abbreviated both as CHT and CH in the manuscript. This should be unified. Please review and standardise the use of all abbreviations throughout the text.

The references are generally current and relevant. However, there is a clear duplication: Reference 1 and Reference 3 both cite the same article.

Author Response

ABSTRACT

Comments 1:The abstract is informative but should explicitly state that the manuscript is a workshop report and expert consensus document, rather than an original research study.

Response 1: Thank you  for pointing this out. We agree with the comments and have effected it on page 1, paragraphs 2 , line 4-8 1n the revised manuscript. 

This manuscript is a workshop report and expert concensus of a three-day national workshop organised by the Newborn Screening Consortium- Nigeria(NSC-N) in conjunction with The Federal Ministry of Health Nigeria, Revvity and international partners. The maiden meeting comprised experts in different fields of newborn screening and newborn care who reviewed priority congenital disorders, implementation barriers and national NBS needs in Nigeria. 

Comments 2:In addition, the abstract presents conclusions and strategic outcomes without explaining how consensus was achieved. A brief mention of the methodology used to synthesize expert input (guided discussions, consensus agreement) would improve transparency.

Response 2: Thank you  for pointing this out. We agree with the comments and have effected it on page 1, paragraphs  3, line 10-12 1n the revised manuscript.

Experts presented pilot data, opinions, and global best practice evidence. Contributions were examined and debated and conclusions were reached by guided discussions and consensus agreement for a pragmatic nationwide NBS plan.

Introduction

Comments3 :The introduction provides a solid overview of the importance of newborn screening and appropriately contextualizes the Nigerian situation within the global landscape. However, statements such as “over 50 conditions are routinely screened globally” should be qualified, as the number of screened conditions varies widely depending on country and resource level. The authors are encouraged to provide more specific data, such as examples illustrating the wide variety of conditions that may be included in newborn screening panels, and to mention conditions that are screened in some countries or regions but not in others, in order to better convey the heterogeneity of global newborn screening practices.

Response 3: Thank you  for pointing this out. We agree with the comments and have effected it on page 2, paragraphs 1, line 5-13 1n the revised manuscript. Newborn screening is not merely a blood test, but a transformative public health service that has been demonstrated to be extremely effective in reducing morbidity^[1]. Globally, more than 60 conditions can be screened for ^[1,3],these vary widely across countries depending on the available resources, level of development, available technology, and disease prevalence. The conditions that are commonly screened for may range from haemoglobinopathies; phenylketonuria (PKU), Cystinosis, Maple syrup urine disease (MSU), transport disorders such as cystitis fibrosis(CF) among many Caucasian communities and metabolic disorders like congenital hypothyroidism(CH) among other numerous conditions. The newborn screening programme in the Philippines that began with five conditions has expanded to a panel that screens at least 19 newborn conditions^[4].

Comments 4: It is recommended to conclude the introduction with a clear statement of the manuscript’s objective, explicitly indicating that the aim is to report the outcomes of a national workshop and propose a strategic framework for newborn screening implementation in Nigeria.

Response 4: Thank you  for pointing this out. We agree with the comments and have effected it on page 2, paragraphs 2 and 3, line 10-12 1n the revised manuscript. The main aim of this report is to document the outcome of the first national workshop on integrated newborn screening in Nigeria and propose a strategic framework for newborn screening implementation in Nigeria and canvass government support.

Comments 5: Organization: The description of participating institutions and stakeholders is comprehensive and informative. Nevertheless, the manuscript lacks a basic description of the workshop methodology. It would be important to clarify: approximately how many participants attended, how the sessions were structured (e.g., plenary sessions, working groups), how decisions and final recommendations were reached. Including this information would enhance the credibility and reproducibility of the consensus process.

Response 5: Thank you  for pointing this out. We agree with the comments and have effected it on pages 2 and 3, paragraph 3 line 1-12 1n the revised manuscript. 

Organisation

The selection of the workshop participants was largely based on the existing 6 health zones in Nigeria, the Federal Ministry of Health, and non- governmental organisations involved in maternal and child health. The workshop was attended by 54 people people drawn from these organisations and was funded by Revvity. The maiden drew experts in the fields of newborn screening and newborn care to review priority congenital disorders, implementation barriers and national NBS needs in Nigeria. The selected experts presented pilot data, opinions, and evidence for global best practice. All contributions were examined and debated, conclusions were reached by guided discussions and consensus agreement for a pragmatic nationwide NBS plan. A follow up meeting of stakeholders was scheduled to hold 6 months after, the second meeting held at the same time and location with the World Sickle Cell congress that took place in Nigeria. It was a follow-up to review the progress of decisions made at the first NSC-N meeting to collaborate with and learn from other countries who had successful newborn screening programmes.

Comments 6: Laboratory perspectives: Advanced technologies such as LC-MS/MS and genomic sequencing are discussed. In addition to what Professor Anetor has said, while scientifically accurate, it should be more clearly stated that current newborn screening programmes worldwide are still primarily based on conventional biochemical screening, including mass spectrometry–based approaches among other techniques, and that genomic screening is an emerging tool that is not yet implemented in the majority of newborn screening programmes globally. Genomic approaches should therefore be clearly presented as a future or complementary strategy, rather than as a requirement for initial implementation. It would be appropriate to support these claims with direct references.

Response 6: Thank you  for pointing this out. We agree with the comments and have effected it on page 3, paragraphs 3, line 4-12 1n the revised manuscript. 

Laboratory perspectives

Professor John I. Anetor, a Chemical Pathologist at the University of Ibadan and the convener of the workshop, delivered a series of presentations outlining the scientific rationale, methods, and policy imperatives for newborn screening (NBS) in Nigeria. In his talk, he said that many inborn errors of metabolism are treatable when identified early. He also reviewed advanced diagnostic platforms, including high-performance liquid chromatography (HPLC), tandem mass spectrometry (MS/MS), and genomic sequencing. Although these advanced technologies are gaining some traction in newborn screening, current newborn screening programmes worldwide are largely based on conventional biochemical screening methods including, immunoassay, colorimetry, fluorometry and mass spectrometry^[8]. Genomic screening is also an emerging tool that is not widely employed in newborn screening programmes^[8]. He stressed that the advanced methods are not limitations to starting a newborn screening programme and may be an expansion plan after the programme in Nigeria is well established.

He proposed a tiered model suited to our local context. In his proposed model, NBS is initiated using simple biochemical assays in the primary setting, with positive cases referred to central reference laboratories. He concluded that a phased implementation and a firm policy commitment are essential for a sustainable national NBS programme.

Comments 7: The importance of early screening and treatment for congenital hypothyroidism is well presented. However, when specific screening windows and treatment timelines are mentioned, it would be appropriate to support these claims with direct references.

Response 7: Thank you  for pointing this out. We agree with the comments and have effected it on page 4, paragraphs 1  line 4 &12 1n the revised manuscript. 

Clinician Perspectives

Professor Ayede, a Consultant Neonatologist at the University College Hospital, Ibadan, and co-team lead, addressed the need to institutionalise and scale up newborn screening systems nationwide. She noted that sub-Saharan Africa contributes to nearly 30% of global congenital anomalies but has weak integrated screening frameworks^[9]. Her presentation called for strengthened institutional collaboration, robust policy formulation, and data-driven planning to reinforce Nigeria’s newborn health structure. She proposed that linking NBS with immunisation and neonatal intensive care would help to achieve coverage.

Dr Oluwakemi Ashubu, a Paediatric Endocrinologist at the University College Hospital, Ibadan, spoke about newborn screening for congenital hypothyroidism, a leading cause of preventable intellectual disability. She emphasised the critical window for screening within 72 hours of life and initiation of levothyroxine therapy within two weeks for optimal neurodevelopmental outcomes^[10,11]. Her talk advocated for the strengthening of national screening and follow-up systems to promote cognitive health in children.

Comments 8:World Health Organization Dr Ayesha De-Costa noted that 90% of children with serious congenital anomalies are born in LMICs and advocated for integrating newborn screening into routine health systems. It is necessary to indicate the original reference.

Response 8: Thank you  for pointing this out. We agree with the comments and have effected it on page 5, paragraphs 3, line 3 in the revised manuscript. 

Dr Ayesha De-Costa, representing the World Health Organization, offered a global perspective on prioritising birth defect screening in low- and middle-income countries. She noted that 90% of children with serious congenital anomalies are born in LMICs^[9], and advocated for

Comments 9: Key Discussion Points It would be important to include basic demographic data on births in Nigeria. Specifically, the authors should indicate approximately how many births occur annually, and whether this number has increased in recent years, as this information is essential to contextualise the scale, feasibility, and potential impact of a national newborn screening programme.

Response 9: Thank you  for pointing this out. We agree with the comments and have effected it on page 6, paragraphs 2 line 3-15 1n the revised manuscript. Given the many candidate congenital conditions eligible for screening in Nigeria, the expert panel agreed that a phased approach would be most pragmatic. Two conditions were prioritised based on their prevalence, clinical impact, and the feasibility of early intervention. These included Sickle cell disease (SCD) and congenital hypothyroidism (CH), which both meet the Wilson and Jungner criteria for population-based screening^[12]. In Nigeria, both conditions contribute to significant early childhood morbidity and mortality, yet remain clinically silent at birth. Their natural histories are well-defined, screening tests are available, and early detection enables low-cost interventions that improve survival and neurodevelopmental outcomes. These support the epidemiological justification for integrating SCD and CH into national newborn screening strategies in Nigeria^[12].

Nigeria’s recent birth rate estimates approximates 7.56 million live births per year^[13,14], reflecting sustained demographic growth and a large newborn population at risk for early childhood disease burdens. The country’s crude birth rate remains elevated, at around 33 births per 1 000 population per year, compared with a global average below 18 per 1 000^[13]. A systematic review and meta-analysis reported a pooled prevalence of sickle cell disease (SCD) of approximately 4 % (95 % CI 3–6 %) among Nigerian children and adolescents, with sickle trait carriers accounting for a significantly higher proportion of the population^[15,16]. A 4 % prevalence applied to Nigeria’s substantial annual birth cohort suggests that over 300 000 infants may be born with SCD each year making sickle cell disease a public health burden.

Prioritisation of Target Conditions

Given the many candidate congenital conditions eligible for screening in Nigeria, the expert panel agreed that a phased approach would be most pragmatic. Two conditions were prioritised based on their prevalence, clinical impact, and the feasibility of early intervention. These included Sickle cell disease (SCD) and congenital hypothyroidism (CH), which both meet the Wilson and Jungner criteria for population-based screening^[12]. In Nigeria, both conditions contribute to significant early childhood morbidity and mortality, yet remain clinically silent at birth. Their natural histories are well-defined, screening tests are available, and early detection enables low-cost interventions that improve survival and neurodevelopmental outcomes. These support the epidemiological justification for integrating SCD and CH into national newborn screening strategies in Nigeria^[12].

Nigeria’s recent birth rate estimates approximates 7.56 million live births per year^[13,14], reflecting sustained demographic growth and a large newborn population at risk for early childhood disease burdens. The country’s crude birth rate remains elevated, at around 33 births per 1 000 population per year, compared with a global average below 18 per 1 000^[13]. A systematic review and meta-analysis reported a pooled prevalence of sickle cell disease (SCD) of approximately 4 % (95 % CI 3–6 %) among Nigerian children and adolescents, with sickle trait carriers accounting for a significantly higher proportion of the population^[15,16]. A 4 % prevalence applied to Nigeria’s substantial annual birth cohort suggests that over 300 000 infants may be born with SCD each year making sickle cell disease a public health burden.

Comments 10:Prioritisation of target conditions It would strengthen the manuscript to explicitly explain how sickle cell disease and congenital hypothyroidism fulfil the Wilson and Jungner screening criteria. What incidence should a disease have in order to be considered for newborn screening?

Response 10: Thank you  for pointing this out. We agree with the comments and have effected it on page 6, paragraphs 2 line 3-7 in the revised manuscript.Sickle cell disease (SCD) and congenital hypothyroidism (CH), which both meet the Wilson and Jungner criteria for population-based screening^[12]. In Nigeria, both conditions contribute to significant early childhood morbidity and mortality, yet remain clinically silent at birth. Their natural histories are well-defined, screening tests are available, and early detection enables low-cost interventions that improve survival and neurodevelopmental outcomes. These support the epidemiological justification for integrating SCD and CH into national newborn screening strategies in Nigeria^[12].

Comments 11: Why have other diseases, such as certain amino acid disorders or beta-oxidation defects, been ruled out? Is their future implementation possible? Perhaps it would be good to indicate this in the text.

Response 11: Thank you  for pointing this out. We agree with the comments and have effected it on page 7, paragraphs 2 , line 12-19 1n the revised manuscript. 

Other rarer conditions in Nigeria, such as fatty acid oxidation disorders, organic acidemias, and other inborn errors of metabolism, were not included in the initial implementation stage of the national newborn screening programme. In addition, conditions such as phenylketonuria, galactosemia, maple syrup urine disease, congenital adrenal hyperplasia, and additional hemoglobinopathies are potentials for future inclusion. These disorders are detectable in the pre-symptomatic period, and have effective interventions. They are therefore suitable for the expansion of the NBS programme as diagnostic capacity, treatment infrastructure, and public health resources improve.

Comments 12: Be careful with abbreviations. For example, congenital hypothyroidism has been abbreviated both as CHT and CH in the manuscript. This should be unified. Please review and standardise the use of all abbreviations throughout the text.

Response 12: Thank you  for pointing this out. We agree with the comments and all abbreviations have been harmonised in the revised manuscript. 

Comments 13:The references are generally current and relevant. However, there is a clear duplication: Reference 1 and Reference 3 both cite the same article.

Response 13: Thank you  for pointing this out. We agree with the comments and all references have been correctre, irrelevant ones were deleted and new ones were also included as new information has become available between the time of the first draft and manuscript revision

 

Reviewer 2 Report

Comments and Suggestions for Authors

1. Introduction – ‘These include inborn errors of metabolism, hemoglobinopathies, immunodeficiency and critical congenital heart disease.’ – Please change for ‘...hemoglobinopathies, severe combined immunodeficiencies and critical congenital heart disease, among others.’. There are other disorders that have been screened for decades, such as cystic fibrosis, and new ones that are being incorporated in NBS programs, such as spinal muscular atrophy, which should be taken into account.
2. Introduction – The authors state that, globally, over 50 conditions are routinely screened for. This is not totally true as there are big differences in the number of disorders that are screened for even in different regions of the same country. Taking into account the Recommended Uniform Screening Panel (RUSP), I would suggest to change this sentence for ‘Globally, more than 60 conditions can be screened for...’. Please change this also in the ‘Key Discussion Points’ section.
3. Laboratory perspectives – ‘tandem mass spectrometry (GC-MS, LC-MS/MS)’ – Please correct this for the standard abbreviation, which is ‘MS/MS’.
4. The abbreviation ‘LMICs’ is correctly defined in section ‘Industry perspectives’, but it is not used is later sections (‘International best practice’ and ‘World Health Organisation’). Similarly, ‘DBS’ is defined in ‘Public health perspectives’ section, but it is not used afterwards. Please also review the use of ‘CHT’ and ‘CH’ abbreviations (‘Prioritisation of Target Conditions’ section).
5. Conclusion Highlight – ‘Newborn screening is not just a diagnostic test...’ – Please change for ‘Newborn screening is not just a detection test...’, as screening tests are used for detection rather than diagnosis.
6. References - There are several mistakes in this section, please review all of them accurately. For example, references 1 and 3 are repeated, PMIDs are not correct for 3, 4, 10 12 and 13, and the journal for reference 9 is not correct.

Author Response

1. Introduction – ‘These include inborn errors of metabolism, hemoglobinopathies, immunodeficiency and critical congenital heart disease.’ – Please change for ‘...hemoglobinopathies, severe combined immunodeficiencies and critical congenital heart disease, among others.’. There are other disorders that have been screened for decades, such as cystic fibrosis, and new ones that are being incorporated in NBS programs, such as spinal muscular atrophy, which should be taken into account.
2. Introduction – The authors state that, globally, over 50 conditions are routinely screened for. This is not totally true as there are big differences in the number of disorders that are screened for even in different regions of the same country. Taking into account the Recommended Uniform Screening Panel (RUSP), I would suggest to change this sentence for ‘Globally, more than 60 conditions can be screened for...’. Please change this also in the ‘Key Discussion Points’ section...................Response: WE agree with these comment and have revised it based on the reviewers suggestions in page 2 paragraph 1 in the revised manuscript morbidity^[1]. Globally, more than 60 conditions can be screened for ^[1,3],these vary widely across countries depending on the available resources, level of development, available technology, and disease prevalence. The conditions that are commonly screened for may range from haemoglobinopathies; phenylketonuria (PKU), Cystinosis, Maple syrup urine disease (MSU), transport disorders such as cystitis fibrosis(CF) among many Caucasian communities and metabolic disorders like congenital hypothyroidism(CH) among other numerous conditions. The newborn screening programme in the Philippines that began with five conditions has expanded to a panel that screens at least 19 newborn conditions^[4]. Nigeria, a nation
3. Laboratory perspectives – ‘tandem mass spectrometry (GC-MS, LC-MS/MS)’ – Please correct this for the standard abbreviation, which is ‘MS/MS’.
4. The abbreviation ‘LMICs’ is correctly defined in section ‘Industry perspectives’, but it is not used is later sections (‘International best practice’ and ‘World Health Organisation’). Similarly, ‘DBS’ is defined in ‘Public health perspectives’ section, but it is not used afterwards. Please also review the use of ‘CHT’ and ‘CH’ abbreviations (‘Prioritisation of Target Conditions’ section).,,,, Response- The abbreviations have been harmonised and corrected in all the highlighted sections.
5. Conclusion Highlight – ‘Newborn screening is not just a diagnostic test...’ – Please change for ‘Newborn screening is not just a detection test...’, as screening tests are used for detection rather than diagnosis. Response,,,, This has been addressed  based on the reviewers suggestions on page 9 line 13
6. References - There are several mistakes in this section, please review all of them accurately. For example, references 1 and 3 are repeated, PMIDs are not correct for 3, 4, 10 12 and 13, and the journal for reference 9 is not correct....... We agree with this review and all references have been corrected, irrelevant references have been deleted and new ones added based on new evidence from the time of the first drat to the time of this revision