PaVIEWPOINTSpers studies inAfrica Systematic reviewofbirthcohort Harish Nair [email protected] Scotland, UK EH89AG Teviot Place University ofEdinburgh Centre forPopulationHealthSciences Dr IgorRudan Correspondence to: 2  1  Igor Rudan Alasdair Campbell 46 global of SplitSchoolMedicine,Split,Croatia Croatian CentreforGlobalHealth,,Scotland,UK and GlobalHealthAcademy,University Centre forPopulationHealthSciences journal of June, 2011 •

and Rajmohan Panda health 1,2 Vol. 1No. 1 www.jogh.org 1 diseaserisk(4–6)manynotabletheyandhavetoled discoveries (7–9). mental,social and environmental exposures that interact in determining countries(2–11). Thesestudies provide useful insight intothedevelop cohort studies have been conducted, and are still ongoing, in high gitudinalincomebirthcohortstudies ( The last two decades have seen a dramatic rise in research output in lon to vaccines and antibiotic treatment. survival of infectious diseases in the first years of life, and response and low birth weight, the links between maternal and infant health, growthine development,and birthoutcomes prematuritysuchas lead to an improved understanding of the determinants of intrauter ourstofoster and develop research capacity for these studies, may Conclusion health and lifestyle data. associated and DNA collecting biobanks cohort birth scale large healthresearch sub-Saharantheyetand African region stillawaits approachgenomicmajorharnesstechnologiestoemergeda in as several rounds of study follow up. Population-based ‘biobanks’ have challenges:forfundingnotably, of lackattrition and of rates high methodological many face studies These storage. for DNA lected biological data, 10 collected blood samples and only one study col Results and were retained for full text analysis. tained only 189 papers, of which 71 met minimum quality criteria papers were retrieved. Application of inclusion/exclusion criteria re tabases: MEDLINE, EMBASE, AFRO and OPENsigle. A total of 8110birth cohort studies in sub-Saharan Africa across the following da Methods suitability as a platform to support genetic epidemiological studies. cohort studies conducted in sub-Saharan Africa and to consider identifydisease.birthreviewtoThisaims ofknowledgecause their on advancing is technologies genomic new employing research of amongstchildrenwomenand continue persist.to emergenceThe Aim In sub-Saharan Africa, unacceptably high rates of mortality of rates high unacceptably Africa, sub-Saharan In The search revealed 28 birth cohorts: 14 of which collected A systematicA literature reviewconducted was identifyto Investment in this field, together with related endeav Figure1 ) (1). Several(1).large)quality birth ------cohort study’ in the past 20 years; no WeblanguageScienceof or other restrictions. of disease from high-income countries to SSA may be lim this, the transferability of research findings on determinants countriesSSAinandSouth EastAsia (12). additionIn to developing large several in concentrated being death’s and 15% of global child deaths respectively, most of these bacterial and diarrhoea which account for 18% vestmentrelative to disease burden) was most notable for disease burden. This mismatch (with very low research in between funding for research and development relative to Sydney,discrepancyin markedHealth tional a observed InternaInstitutefor the at (14), al et Moran by study A Figure 1 tality (2,12,13). health concerns, withpublic anmajor unacceptably still are children and women of diseases maternalcomplications pregnancyofcommunicable and countries, (SSA) African sub-Saharan In (13). countries many by met being not are 2015, before thirds two by lined in the Millennium Development Goals to reduce this al child mortality has fallen since 1990, yet the targets out (4.20 million) of the deaths occurred in Africa (12). Glob (68%)werecausedinfectiousby diseasesnearly andhalf milliondeaths;5.97millionchildestimated 8.8an were thereresearch. 2008 of neglectedfield In beenfromthis largely mortality, have global of terms in burden health greatest the represent poor,which the of diseases Many developed world. publichealthimportance,ofeasesthe amongst adultsin have focussed mainly on studying the major common dis (11), Biobank UK the as such underway.studies, These morethan 500 recruiting studies and recognition in growing is design logical and genomic data by using large scale cohort study combiningofepidemiovaluediseaseshuman The(10). environmental and lifestyle factors underlying multifaceted vestigation of the separate and combined effects of genetic, gies, with the aim of providing resources for the future in most successful way of harnessing new genomic technolo In recent years, large ‘biobank’ studies have emerged as the Number of publications resulting from a search of the ISI database foranyarticle containing theterm‘birth

000participants are already established or high burden of mor

------The aims of this review were 3-fold: graphical representation in this area of research. eas of the world and there is a clear need for broader geo tries fail to represent the conditions in poverty stricken ar (15). Birth cohort studies conducted in high cancer) income prostate coun and breast (eg, disease communicable municable disease (eg, malaria, HIV, tuberculosis) and foundnon- which determine genetic susceptibility to both com different distributions of genetic polymorphism have been ited.For example, between African and European studies riod of time (months to decades) ( cords, etc.) surveillance, with follow up over a re variable (hospital pe passive and/or etc) examinations (medical active by time, similar a at born people of group a from We defined a birth cohort study as a study collecting data Inclusion/exclusion criteria ing databases (Figure 2): study, a systematic search was conducted across this the to followpertinent keywords and headings MeSH provide After initial scoping exercises and input from a librarian to Search strategy METHODS study. each to relating publications all necessarily not and ies The aim of this search was to identify all birth cohort stud for further studies. Reference lists of finally selected papers were hand searched tional results. informalAn searchGoogle ofScholar produced addino 3. 2. 1. 3) 2) 1) 2010, using the strategy outlined in August 19 on onwards) (1980 Embase and 2010 July 30 on onwards) (1950 Medline OVID: via  the existing literature. on the findings of this review and in the context of tainability of support for this area of research based to offer recommendations on the feasibility and sus lected from birth cohort studies in SSA; col data the andmethodology oftheexamine to study, and follow up frequency); teristics of these studies (population size, length of discussfromandiesSSAimportantsome charac to provide a systematic review of birth cohort stud gust 2010, using ‘birth’ and ‘cohort’ as keywords. search of grey literature: via OpenSIGLE on 22 Au word; AFRO on 22 August Index: 2010, using ‘cohort’ Regional as a key Library Health Global the via Systematic reviewofbirthcohortstudiesinAfrica www.jogh.org June, 2011 • Table 2 ). Initial inclusion Table 1 Vol. 1No. 1 ; 47 ------

VIEWPOINTSPAPERS PaVIEWPOINTSpers aspects of data collection. ysis in order to focus further on quantitative and qualitative Studies that met the criteria were retained for full text anal appliedto studies in a follow-up to the initial assessment. For more specific birth cohort analysis, strict criteria were collectinglongitudinalinfancy/childhoodin data SSA. in characteristicsprovidingtheoverview inofstudies anof meeting strict definitions of birth cohort studies, are useful necessarily not whilst which, studies longitudinal trieve criteria were sensitive but not specific, so that we could re omies (July 2010) as low- or middle-income. Developing countries were those defined by the list of econ *WithintermswerecombinedallBooleanboxwitheach operator OR. Alasdair Campbell Table 1 48 4.  3. famil*cohort*.ti,ab. 2. (pregnan* adj3cohort*).ti,ab. 1. (birth*adj3cohort*).ti,ab. 12. (lowadj2middleincomecountr*).tw. 11. middleincomecountr*.tw. 10. lowincomecountr*.tw. 2. 1.expDevelopingCountries/ (birth* adj3longitudinal).ti,ab. comoros/ or madagascar/ or mauritius/ or seychelles/ or fiji/ or fiji/ or papua newguinea/orvanuatu/palau/samoa/tonga/ seychelles/ or mauritius/ or madagascar/ or comoros/ transcaucasia/ or armenia/ or azerbaijan/ or “georgia (republic)”/ or exp or / or ukraine/ or serbia/ or russia/ or romania/ or or byelarus/ or “macedonia (republic)”/ or moldova/ or montenegro/ bulgaria/ or bosnia-herzegovina/ or lithuania/ or albania/ or golia/ people’socratic mon- korea”/or “republicof korea”/ or republic of or nepal/ or pakistan/ or sri lanka/ or exp china/ or korea/ or “dem- or iran/ or iraq/ or jordan/ or lebanon/ or syria/ or turkey/ or yemen/ afghanistan/ or sikkim/ or india/ or bhutan/ or bangladesh/ or ern/ or myanmar/ or philippines/ or thailand/ or vietnam/ or asia, west- stan/ or cambodia/ or east timor/ or indonesia/ or laos/ or malaysia/ kazakhstan/ or kyrgyzstan/ or tajikistan/ or turkmenistan/ or uzbeki or peru/ or suriname/ or uruguay/ or venezuela/ or asia, central/ or or brazil/ or chile/ or colombia/ or ecuador/ or guyana/ or paraguay/ panama/ or panama canal or zone/ or mexico/ or nicaragua/ argentina/ or bolivia/ honduras/ or guatemala/ or salvador/ el or rica/ costa or belize/ or grenadines”/america/ the central and or vincent “saint or lucia/ saint or nevis”/ and kitts “saint or jamaica/ or haiti/ or dominica/ or dominican republic/ or grenada/ or guadeloupe/ or senegal/ or sierra leone/ or or togo/ or nigeria/ “antigua or and barbuda”/ or niger/ cuba/ or mauritania/ or mali/ or liberia/ or bissau/ guinea- or guinea/ or ghana/ or gambia/ or d’ivoire/ cote or verde/ or zimbabwe/ or africa, or western/ benin/ or burkina faso/ or cape mozambique/ or namibia/ or south africa/ or swaziland/ or zambia/ or malawi/ or lesotho/ or botswana/ or angola/ or southern/ africa, kenya/ or rwanda/ or somalia/ or sudan/ or tanzania/ or uganda/ or or ethiopia/ or eritrea/ or djibouti/ or burundi/ or eastern/ africa, or gabon/ or guinea/ equatorial or congo”/ the of republic cratic “demo or congo/ or chad/ or republic/ african central or eroon/ or tunisia/ or “africa south of the sahara”/ or africa, central/ or cam- africa/ or africa, northern/ or algeria/ or egypt/ or libya/ or morocco/ June, 2011 • Search strategy for Medline and Embase* Birth cohort

and IgorRudan Vol. 1No. 1 Developing countries www.jogh.org AND OR 8. panelsurvey*.ti,ab. 7. panelstud*.ti,ab. 6. 5.  Longitudinal studies cohort* survey*.ti,ab. Longitudinal Studies/ - - - - - Table 2 Figure 2 relevant to birth cohorts in sub-Saharan Africa other results methods/ type study quality Stage 2 • • • • Stage 1 Inclusion criteria     African Region inWHOSouthSaharan country or meta-analysisofstudies or insighttomethodology reporting results primary low andmiddleincomecountries or qualitativereview ofbirthcohort. nal population or cross sectionalstudyoflongitudi- birth cohort/longitudinalcohort

Inclusion and exclusion criteria for assessing the studies Summary of the literature search. criteria exclusion inclusion/ See Duplicates follow up* selection or population, study cohort detailing of Incomplete reported or methods No results not human Subjects cohort Pregnancy nal study longi-tudi Not a EXCLUSION REASONS FOR n =7405 Excluded - review ofthe screened for Excluded n =516 Systematic n =8110 Titles and relevance abstracts literature countries inWHO abstract analysis Excluded n =118

Selected for SSA region Limited to n =705 Exclusion criteria • • • • • Stage 2–Qualitycriteria Stage 1      age atinduction less than60monthsof of 500 minimum cohortsize of followup minimum of12months weight followup study limitedtobirth primarily apregnancy of age enrolment at>10years exclusion criteria children 124 S

Application tudies inclusion/ of further S longitudinal tage

from in

1 young

ssa 28 birthcohort S

elected

paper studies n =71 S tage

review

for 2

full

in The study characteristics of the full paper reviews are found Study characteristics – Stage 2 setting were conducted in the community. cific population. The large majority of studies identified for Methods: frequency and full text analysis was needed. two-yearly. Most abstracts did not report data on follow up Frequency: cohort for 2 years or less. The majority of the studies (n = 63), however, followed the followed the initial cohort for 20 years and is still ongoing. Twenty’longestSouththeAfricastudyrunning,inis has ticipants ranged from 3 months to 20 years. The ‘Birth To antenatalperiodbirth.at or Thefollow period uppar of Followup: participants) suggested in this study. (500 criteria quality the than less recruited 59 duction. pants and only 27 studies recruited more than 1000 at in ticipants.studiestheofrecruited 79 lesspartici1000or Study size: Study characteristics – Stage 1 characteristics ( ing Stage 1 criteria. Abstracts were analysed for basic study longitudinalcohort studies ( 124producedfrompapers data189 Abstract analysisof R odological challenges; and attrition. other developmental indicators; socioeconomic data; meth urine);anthropometric data; cognitive, psychological and and DNA blood, as (such samples biological to, limited ies were assessed by categories that included, but were not Both qualitative and quantitative data were assessed. Stud hensive. infull andthe data obtained wasintended tobecompre includedies fullforpaperreview (Stagewere2) assessed ratherthan provide comprehensive data extraction. Stud vide background perspective of longitudinal studies in SSA and analysed by abstract alone. This exercise aimed to pro Studies included in Stage 1 were extracted to an Excel file Data extraction 1272, ranging from 571 to 11 is induction at participants of number median the sis, Study size: relate to these 28 studies. data for 28 separate birth cohort studies. All further results ESULTS Table4 48 studiesidentified werespe 48followed that a .Analysis of 71 full text publications produced

The study sizes ranged from 30 to 11,342 par Of the 28 studies retained for full paper analy 53 studiescollectionbegan53data the either in Frequency of follow up rangedfromFrequencytodaily followup of Table 3 ). Table3

342. and Figure3 )meet

------Blood: Biological measurements cord blood (n = 5), 8), = (n bloodincluding:maternalsamples, blood other ticipants ( induction was 17 months. induction:at Age monthly, ranging from bi-weekly to five annualy. 12 to 216 months. Median frequency of follow up was bi- Follow up: ran Africa (SSA) † Details not presented in abstract. * Sometimes varied between publications. Table 3 Specific population Setting (months) Follow upfrequency (months) Duration offollowup enrolment (months) Maximum ageat Size ofstudy* C haracteristis Characteristics of 124 birth cohort studies in Sub-Saha

Tentheofstudies collected blood from study par Table 5

Median follow up was 24 months, ranging from ). A number Systematic reviewofbirthcohortstudiesinAfrica

www.jogh.org June, 2011 • placental blood (n = 3) and blood smears The mean age of study participantsstudyof ageat mean The Other Not specific population Intervention Malnourished/ underweight Malaria endemicarea toHIV+mother Born Not reported† Facility based Community based Not reported† >6 monthly 2–6 monthly Monthly Weekly Daily Not reported† >120 96–120 73–96 49–72 25–48 0–24 Not reported† >60 49–60 37–48 25–36 13–24 0–12 Antenatal-birth Not reported† >2500 2001–2500 1501–2000 1001–1500 501–1000 0–500

of these ten studies also took Vol. 1No. 1 studies N o 12 76 19 71 46 74 15 17 13 31 13 64 22 10 12 14 53 26 11 22 49 49 . 2 6 9 7 5 1 5 3 1 7 3 5 5 4 6 6 of

- -

VIEWPOINTSPAPERS PaVIEWPOINTSpers frequently used questionnaire based data collection. most variables psychological and status socio-economic Measurementables.nutrition,cognitiveof development, Other data: ly used growth references. tional Centre for Health Statistics were the most common metric measurements. The World Health Organisation/ Na Anthropometry Thirteen of the 28 studies collected no biological data at all. Verybiologicalotherstudies.fewsamplesby taken were Other biological samples pants. currentlyand2005particisamples2200 hasinfortion ‘Birth to Twenty’ study in South Africa began DNA collec HIV status, 1 to detect malaria and only 1 stored DNA. The DNA samples. Five studies collected DNA: 3 were to assess DNA: status and Giemsa stain for malaria. performed on samples were ELISA and Western(n = blot5). Analysisfor HIVof samples varied. The Alasdair Campbell 50 June, 2011 • most of the longitudinal studies in SSA did not take Figure 3 which met full quality criteria. One paper was not presented due to multiple locations of study site. studieseachincountry (out124birthofcohorts). Bluespots relate thespecificto locations cohorts the 28 of Only one study measured psychological vari

and IgorRudan :

18 studies detailed methods of anthropo Number of birth cohort studies in Sub-Sahran Africa (SSA) by country. Coloured boxes refer number of Vol. 1No. 1 www.jogh.org

most common tests ------in 4 studies, 11–20% in 1 study 72.9%.Attritionattrition 10%ratesfollows:weretoas 0 rangingto28% frommedian0%of a has followlastup, Attrition in SSA birth cohorts, measured from induction to Loss to follow up 18 months of follow up. to a rate of loss to follow-up of only 4 percent over the first portationto and from the study clinic, which contributed also provided free medications, immunizations, and trans 18.9%in1992 to7.7% in1994). The Asembo Bay study from attrition reduced (this mothers to given was items care baby containing pack gift a and participants all for theAsembo baycohort study provided free health clinics vided participants with basic mobile phones to aid contact; ing participants with incentives – eg, ‘Birth To Twenty’ pro Effortstopromote successful follow upincluded: provid ure of researchers to retrace study individuals. present for one follow up, but return for the next) and fail participate,refusalto maternalattritiondeath,wave (not tion included: high infant mortality rates, family relocation, Problems reported by studies leading to high rates of attri studies did not clearly report loss to follow up. 40% in 3 studies and more than 40% in 4 studies. Twelve , 21–30% in 4 studies, 31– - - - - - § Reporting of study size varies (1570, 942 and 833); 942 reported in first paper, so this value taken. ‡Data not reported. †Publication year. *Attrition at last recorded study of initial cohort. Attrition varied by study outcome. PC = prospective cohort, RC = retrospective cohort Table 4 Hauspie 1989 Greenberg 1991 Adjorlolo-Johnson 1994 Carme 1992;1994 Guillo duBodan1984 Carme 1984; Ryder 1994b Ryder 1994a; Van Lerberghe 1986 Fegan 2007 Kristensen I2000 1992 Lindtjorn Byass 2008 Lesaffre 1999 Alemu 1996;Asefa1998; Cohen 1976 ter Kuile2003;vanEijk2002 Oomen 1979 Nokes 2004;Ochola2009 McElroy 1999;McElroy 2000;McElroy 2001 Malhotra 2009 Chilongozi 2008 Maleta 2003 Elguero 2005 Vella 1993;Vella 1994 Rayco-Solon 2004 van Yach 1991 Thandrayen 2009; Vidulich 2006; Whati 2005; 2009; Sheppard 2009; Steyn 2000; Steyn 2006; Richter 1995; Richter 2006; Richter 2007; Sabet 2010; Naicker 2010; Norris 2009; Pedro 2008; MacKeown 2003 MacKeown 2007; Martorell Heerden 2010; Jones 2008; MacKeown 2000; Adair 2009; Ellison 2000; Griffiths 2008; McDowell 1982 Reid 1990 Kristensen 2006 Simondon 1998 R efe r ence Characteristics of studies included for analysis Congo Republic of Democratic Congo Republic of Democratic Cote d’Ivoire Congo Congo Congo Republic of Democratic Congo Republic of Democratic Kenya Guinea-Bissau Ethiopia Ethiopia Ethiopia Lesotho Kenya Kenya Kenya Kenya Kenya Zambia Tanzania, Malawi, Malawi Senegal Uganda The Gambia South Africa Zambia South Africa South Africa Senegal C ount r y ‡ Kinshasa Abidjan Linzolo Linzolo Kinshasa Kasongo ‡ ‡ Dubluk/ Elka Butajira Jimma ‡ Kisumu Machakos Kilifi Asembo bay ‡ Lungwena Arua West Kiang (Soweto) Johannesburg ‡ Prieska Soweto Niakhar ‡ ‡ L ocation

1977 1986 1990 1981 1984† 1986 1974 2004 1990 1989 1987 1992 1969 1996 1974 2002 1992 2002 1995 2001 1987 1950 1990 1989 1970 1932 2000 1983 Y ea r prospective prospective prospective retrospective retrospective prospective prospective prospective prospective prospective prospective prospective sectional cohort/ cross prospective prospective prospective prospective prospective prospective prospective prospective retrospective prospective birth cohorts analysis oftwo prospective retrospective prospective prospective spective/ mixed retro- T ype

study of

coho r t

11342 en 4030 2424 1003 1091 4273 3500 8752 1884 1563 1317 2383 1072 3981 3273 1342 1227 1650 942§ C size 587 619 828 661 568 635 586 767 571 r oho o l ment

Systematic reviewofbirthcohortstudiesinAfrica at r www.jogh.org June, 2011 • t

M and birth at antenatal (mother) 0 /birth (

aximum record en months period birth birth birth birth birth birth birth birth birth birth r o 48 60 59 60 60 60 60 60 l ment 9 0 0 0 0 0 0 0

age )

ongoing oct 97 F death/ ( o months ll 216 120 ow 48 18 24 60 36 12 24 20 24 12 60 12 22 12 48 36 36 12 24 48 24 60 12

up )

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up

A tt 72.9 32.5 46.8 28§ 51 (%) 4.4 r 26 14 46 32 10 28 34 44 21 0† ition 4 ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ *

VIEWPOINTSPAPERS PaVIEWPOINTSpers Table 5 atic way. Also, they very rarely (if ever) collect and store andcollect ever)way. (ifaticrarely very they Also, tings and they weren’t planned or organized in any system numberofefforts doexist, they evolved intheir local set areaofresearch. The study clearly shows that, although a this for plans future about recommendations making to absenceof biobank studies in this region and with aview methodologies and the challenges they face – in light of the Thisreview examined birthcohorttheir studies –SSA in D majority of the studies reviewed. the for feasible or appropriate not werehowever, sures, mea These systems. computerised in stored formation between phases of data collection and detailed contact in studystandardisation,sitesallwithtactfor shortperiods moderncommunication systems, close and frequent con Other factors contributing to successful follow up included Y – yes, N – no Alasdair Campbell 52 Adjorlolo-Johnson 1994 Ryder 1994b Ryder 1994a; Greenberg 1991 Chilongozi 2008 van Eijk2002 ter Kuile2003; Malhotra 2009 TOTAL Nokes 2004;Ochola2009 2005; vanYach 1991 Thandrayen 2009;Vidulich 2006;Whati Sheppard 2009;Steyn2000;2006; Richter 2006;2007;Sabet2009; Norris 2009;Pedro 2008;Richter1995; 2007; Martorell 2010;Naicker 2000; MacKeown2003; Heerden 2010;Jones2008;MacKeown Adair 2009;Ellison2000;Griffiths 2008; McElroy 2001 McElroy 1999; McElroy 2000; Rayco-Solon 2004 iscussion June, 2011 •

An overview of the studies that collected biological samples

R and IgorRudan eference Vol. 1No. 1

www.jogh.org ternal blood M N N Y Y Y Y Y Y Y Y 8 a -

blood C N N N N N ord Y Y Y Y Y 5

cental blood pl B N N N N N N N Y Y Y 3 lood a -

sample spring blood O 10 Y Y Y Y Y Y Y Y Y Y ff -

plasma pl serum serum serum asma - - - - - Y – – – – – – / B smear lood N N N N bers of papers are produced, over long periods of time, of periods long over produced, are papers of bers Due to the longitudinal nature of cohort studies large num search criteria was not optimised to retrieving thesethe of design studies.the suggest may it applied,were strictions sophonepopulations Africa.in Although language no re none in Portuguese, despite the large Francophoneand French,and in retrievedLu were papers two Only missed. however, possible that some sources of grey literature were othergrey literature produced Europein until 2005. is,It accesssourcebibliographicalof references reportsofand tem for Information on Grey Literature in Europe) an open searchingforunpublished literature by viaOpenSIGLE made (Sys were bias publication overcome to Attempts Study limitations biochemical studies. and geneticfurther for frozen plasmaand material DNA Y Y Y Y Y 5 –

cell counts. peptide tests,flowcytometry, blot,synthetic ELISA, western infants. randomly selected seropositive blot. Cord-blood from 64 ELISA, confirmed by Western Screen for HIV-1 antibodies by Capillus HIV1-HIV2tests for hb,serostrip HIV-1/2 and malaria smear, Haemocue Finger prickforHIVtest, ELISA, western blot. ELISA, western plasma viralload. blood count,CD4cell blottest,complete western Syphilis screen, ELISAor ELISA Microscopy: giemsa Hb levels:“hemocue”, turnover markers. turnover HIV status,vitDandbone Lead, glucose,insulin,cotinine, Non fastingsample-lipids. and recombinant cytokines. (HemoCue). Antigens,mitogens microfilariae, Hblevels filter for Wuchereria bancrofti Immunoglobulims, antibodies, S ample

anal ysis of age 12 and18months post partum pregnancy, 1 month blood), (maternal Pre-inclusion Birth Birth years. 13 yearsand14 Birth, 5years, Birth F F ixed – – – requency

of

sampling Three monthly (blood film) Two weekly (finger prick) Monthly Six monthly O ngoing – – – – – - - - - with a specific outcome of interest (16). Small sample siz participants thousand twenty of order the of are studies ommended sample sizes for gene-environment interaction thousand,evenortensthousands,of individuals.of Rec calgenomewide association studysizes comprise several SPAC) which studied 13 (AL Children and Parents of study Longitudinal Avon similar birth cohort studies in developed countries such as However,relativelyofis it smallscale whencompared to best example of a large scale, long term birth cohort in SSA. theirchildrenstillongoingis1990and today.in theis It followingunselectedan population 3275ofmothers and The 5000. cohort studies were identified with study sizes greater than samplesizesvarying from11 to571 withactivefollowup, periodsshortofsamplewith sizes largelysmallrestrictedarecohorts birthto SSA the ond, related outcomes in offspring of HIV positive mothers. Sec thanrepresentative population samples eg,assessing HIV cohort studies researched a specific sub-population rather Thisreview demonstrated, first, that the majority of birth important causes of child health and development. studying of purposes the for collection data biobank for monthsofage) withview a toidentifying studies suitable least 12 months of follow up and enrolment at less than 60 mum enrolment of 500 or more study participants with at group of twenty eight studies that met strict criteria (mini frequency of these follow ups. This review identified a sub ticipantsenrolment,at durationthetheandfollow upof includethestudy sizeenrolment,at thestudyageof par descriptiveelementsconsidered review importantthisin of a group of people born at, or around, the same time. The inition is generally recognised as the longitudinal follow up by the different definitions of birth cohort studies. The def Comparabilityacross birthcohortreviews complicated is Study quality rent descriptions of birth cohort studies. have helped to indentify the most comprehensive and cur er than a genuine lack of samples. Writing to authors may tion reflect unreported data or failure to capture data, rath of this study about the lack of good biological data collec studysub-populations. possibleisIt that conclusionsthe studies continue to develop over time in their methods and oftenreporteddifferently betweenpublications cohortas tusof a study was not identified. Study characteristics are a single cohort. It is, however, possible that the current sta allthedataacross thespread publicationsof arising from capturerecentparticulardescriptiontoany andstudy of sizes)andcitation mapping, inorder toidentify themost study,both by hand (matching authors, years and sample by papers group to made study.were Effortsindividual challenging to capture the most updated description of an frommultiple rounds of study follow up. It is, as a result, ‘ Birth to Twenty’began Africato SouthBirth in study

971 births at induction (2). Typi

342.birthOnlytwo

------riskand the potential todiscover disease causing variants ing for more precise mapping of loci associated with displaydisease shorter linkage disequilibrium (LD) blocks, allow have been small (1.5 or less) (20). People of African origin studiedhigh-incomemainlygeneticin–loci countries – risks (or odds ratios) for complex diseases associated with genetically diverse region in the world. To date, the relative Africa, where all human populations originated, is the most pharmacogenomics (18,19). and sequencing genome whole of prospect the and ies nome project, emergence of genome wide association stud highincome countries with completion of the human ge progressrapiddiseaseinstanding madeandbeenof has underrevolutionizedourhave studies genomic Human Biological data identified in this review. studies SSA the to apply also limitations These cohorts. those variables which were collected consistently across the thestudies resulted inrestriction oftheir analyses toonly periods captured by each study. These differences between ferent ages for which data are available; and different time variabledefinitions measurementin and techniques; dif es identified by the COHORTS group included differences the data sets of these studies pooled. Some of the challeng yearsfollow15wereofupincluded this initiativein and withsample sizes 2000ofmoreor newborns andatleast cohorts birth prospective largest five The (17). resource initiative does not include the creation of a large biological ResearchTransitioningin Societies (COHORTS), thisbut as part of the work of the Consortium of Health Orientated largestthemiddle andlowincome country birthcohorts fromdatatogether bring to made beenEfforts haveods. ences in birth cohort study design and measurement differinherentmeth to due data of meta-analyses conduct or therefore,studies.is,It difficult combine study to results differentbetweengreatlymeasurements vary and cohort Finally,there is no single coordinated definition of a birth and adult health. encedevelopmentalof factors futureon child, adolescent which to draw conclusions relating toon the longtime term influof amount insufficient an years, two than less Third, the large majority of studies followed the cohort for and adult health. encedevelopmentalof factors futureon child, adolescent which to draw conclusions relating to the long term influ forless than twoyears, aninsufficient amount of time on Second,largethemajority studies of followed cohort the opment outcomes in pregnancy and early childhood. genetic and environmental influences of health and devel the study to whichupon securebasis provide a tolikely un are review Africanthis studiesidentifiedthe in of es Systematic reviewofbirthcohortstudiesinAfrica www.jogh.org June, 2011 • Vol. 1No. 1 53 ------

VIEWPOINTSPAPERS PaVIEWPOINTSpers requirestorageexport andprocessingfor highincomein cilities in most sub-Saharan African countries, samples may for harm (26). Due to the lack of large scale genotyping fa tion about an individual or population which may be used potentialstudiesrevealthehavestigmatisingto informa of study participants is an essential consideration as GWA their level of education and literacy. Protecting the privacy of regardless participants, study by made be can choice obtained in a way that ensures an informed and voluntary portant ethical considerations (25). Valid consent must be Genome-based studies in developing countries present im new research opportunities and development in SSA. ever, foster local capacity building and drive innovation for Thecomplexity ofundertaking these studies could, how (23). risk disease termine interactratherenvironmentaltheywith exposuresde to alone, susceptibility disease chronic for account not do EuropeanfactorspopulationsGenetic(21,22). in blocks LD large by masked been have previously may which Alasdair Campbell tainedonly2 took DNA samples to establish a DNA bank, and this con problemsof SSA. Only one of the birth cohorts identified lifestylefactorsunderlying childhealthdevelopmentand collected birth cohort data on genetic, environmental and systematicallyof lackhighlight the to reviewserves This many exciting presents possibilities for genetic research. pressures selection natural and sures environmentalitsdiversity, with bined expo lifeunique state-of-the-art facilities and run by well trained staff (22). with equippedare laboratorieswhich to accesssamples, gent quality criteria for complex processing and storage of er income countries (21). DNA based studies require strin ical and genomic research capacity between SSA and high children in Africa. However, a gaping divide exists in clin edgeabout communicable diseases amongst mothers and world biobanks have the potential to generate new knowl The same technologies which are being used in developed power and laboratory facilities to do so. nativedata collection, or a simple lack of resources, man ples of any sort reflecting either a primary interest in alter Overall,theofstudies1328 collected biologicalno sam 37.02 in Germany). and UK in 68.15 USA, in 205.5 (eg, countries income combined (0.34), is insignificant compared to thoseare inputs of country SSA high all when even studies, sociation tionof sub-Saharan African countries to genome wide as Thesecomparative weightings showedcontributhethat (24). al. Rosenburget by study a in origin of country to searchInstitute catalogue were assigned weight according Re Genome Human National the in contained articles nostic assessment of HIV or malaria status. The 473 GWA ples taken by studies were one-off measurements for diag 54 June, 2011 •

and IgorRudan 200individuals. Themajority DNAofsam Vol. 1No. 1 www.jogh.org

Africa’sdiversity,genetic com ------

77% of the original cohort. retraced 2005 in up follow and attrition limited Pelotas sampling, army enlistment and the low emigration rate in today.ongoing Household still is and world developing one of the largest and longest running birth cohorts in the suringover 4000 variables for 5914 study participants, is study1982,(31).thiswhichmeaThebeganintoment studies such as the Pelotas birth cohort in Brazil are testa nal cohorts in the developing world they are achievable Despiteand the methodological challenges faced by longitudi all homes in the study area to retrace study participants. mation, army enlistment days and systematic searching of population. Other studies have used national census infor suchthattheylongerareno representative normaltheof ever, there is a risk of subsequently conditioning the cohort ticipants with incentives to continue with the study, how Efforts to overcome attrition have included providing par the original population from which it was taken. tentiallyresultingsamplelonger noarepresentative in of ban section of a cohort may be more likely to migrate, po to longitudinal studies especially as the more educated, ur data collectors. High rates of migration also pose a challengewidespread challengepatient identifiers a to pose SSA in as such aids ministrativeanddatabasescentres,national common cause of attrition (30). Lack of infrastructure, ad world,failuretrace individualsto reportedismostthe as developing the In results. of interpretation and lection up. Both have the potential to cause systematic bias in col are reported: initial non-enrolment and attrition on follow es to researchers. In birth cohorts two types of sample loss Longitudinal studies pose unique methodological challeng in low-income countries Challenges of longitudinal studies of 500 of logical samples for biobank data. The UK Biobank, a cohort sources of funding if birth cohort studies are to collect bio rounds of follow up. There is a particular need for multiple funding for initiating studies and then supporting attracting in multiple difficulty report studies cohort birth Most Funding in malaria research has shown (25). these challenges can be successfully met as the experience However,process.challenging and complex a standably f archivedofsamples useObtaining(29). ethical approval required limiting the ability for secondary analysis and re- destructionhandlingsampleoftenguidelinesandare on researchStrict(28). inrelease andsharing data for need the and privacy participant’s study of protection tween be struck is balance a thatessential is It (27).countries or genomic research in developing countries is under is countries developing in research genomic or

000 people with a baselineyearassessmentpeopleawith 000 8 and

------subsequently stimulate economic development. may and SSA,research clinicalin andacademic of ment infrastructure,tionizingthefuturedevelop trainingand tial. They will, however, have a long term effect by revolu foralarge scale SSA study. Such investments are substan 9.8–449)14–644(€comparedUS$ 18) to (€ 26 US$ to The cost per person per year for the UK Biobank estimate foracohort of 400 billion)1.8billionacross 2.56(€ three countriesUS$ or 150 of cohort a for million) 16.5 (€ million pacity building – would cost anywhere between, US$ 23.7 posure measurements, intervention trials and research ca study similar to the UK Biobank in SSA with additional ex Onestudy estimated that the cost ofsetting uptena year west Regional Development Agency and others. Scottish Government, British Heart Foundation, the North MedicalResearch Council, theDepartment ofHealth, the (the UK’s largest independent medical research charity), the lion) (32). The UK Biobank was funded by Wellcome Trust follow up is projected to cost US$ 104 million (€ 72.5 mil

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------: A lifecourse approach to coronary heart disease prevention scientific . Examining life-course influences on chronic disease: the importance of avoidable mortality is centred. future of mothers and children upon whom a large burden research capacity of SSA, and in doing so, investing in the turnedtheytimetheirresources towards investingthe in banks in high-income countries. We suggest that it is now agencies have made large investments not-for-profit towards and Governments funding SSA. in bio biobanks such sustainabilityensureestablishdressedthenthetoand of initialtheoffewchallenges arejusta ad bethatneedto assessmentity locatingandsourcestermlong funding of studies alongside the creation of ethical frameworks, qual pilot and infrastructure training, research in Investment lated health data was identified but this was of a studysmall which scale.systematically collected DNA samples cohort and birth re one Only (34–91). Africa in sites 28 from Thisreview identified larger a number of relevant studies C onclusion

” www.icmje.org/coi_disclo Systematic reviewofbirthcohortstudiesinAfrica www.jogh.org June, 2011 • - - Vol. 1No. 1 55 - - - - - .

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