Effects of early interventions focused on the family in the development of children born preterm and/or at social risk: a meta-analysis 夽,夽夽

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JPediatr(RioJ).2020;96(1):20---38

www.jped.com.br

REVIEW ARTICLE

Effects of early interventions focused on the family in the development of children born preterm and/or at social risk: a meta-analysis ^夽,夽夽

Rachel de Carvalho Ferreira

^a^,∗

, Claudia Regina Lindgren Alves

^b

, Marina Aguiar Pires Guimarães

^c

, Kênia Kiefer Parreiras de Menezes

^d

, Lívia de Castro Magalhães

^e

aGrupoUniversidadeBrasil,FaculdadeSantaLuzia,DepartamentodeFisioterapia,SantaLuzia,MG,Brazil

bUniversidadeFederaldeMinasGerais(UFMG),FaculdadedeMedicina,DepartamentodePediatria,BeloHorizonte,MG,Brazil

cUniversidadeFederaldeMinasGerais(UFMG),ProgramadePós-Graduac¸ãoemCiênciasdaSaúde---SaúdedaCrianc¸aedo Adolescente,BeloHorizonte,MG,Brazil

dUniversidadeFederaldeMinasGerais(UFMG),EscolaEducac¸ãoFísica,FisioterapiaeTerapiaOcupacional(EEFFTO), DepartamentodeFisioterapia,BeloHorizonte,MG,Brazil

eUniversidadeFederaldeMinasGerais(UFMG),EscolaEducac¸ãoFísica,FisioterapiaeTerapiaOcupacional(EEFFTO), DepartamentodeTerapiaOcupacional,BeloHorizonte,MG,Brazil

Received10December2018;accepted6May2019 Availableonline27June2019

KEYWORDS Earlyintervention (education);

Parents;

Childdevelopment;

Infant;

Prematurenewborn;

Riskfactors

Abstract

Objective: Toverifywhetherearlyinterventionfocusedonthefamilyimprovesthecognitive, motor,andlanguagedevelopmentofchildrenbornpretermand/oratsocialriskintheﬁrst3 yearsoflife.

Sourceofdata: Meta-analysisofclinicaltrialspublishedbetween2008and2018,inthefol- lowingdatabases:CINAHL, MEDLINE---PubMed,MEDLINE ---BVS,LILACS---BVS,IBECS ---BVS, PEDroandCochraneReviews.Experimentalstudiesonearlyinterventionsfocusedonthefam- ily,whosetargetgroupswerechildrenbornpretermand/oratsocialrisk,withassessmentof cognitiveand/ormotorand/orlanguagedevelopmentupto3yearswereincluded.Thestudies wereratedusingthePEDroScale.

Datasynthesis: Twelvestudieswereincludedfromatotalof3378articles.Earlyintervention focusedonthefamilycontributedtothe developmentofthecognitive(StandardizedMean Difference---SMD=0.48,95%CI:0.34---0.61)andmotor(SMD=0.76,95%CI:0.55---0.96)domains ofpreterminfants.Regardingcognitivedevelopment,performanceimprovementwasobserved at12,24and36months,whileinthemotordomain,theeffectwasobservedonlyat12monthsin

夽 Pleasecitethisarticleas:FerreiraRC,AlvesCR,GuimarãesMA,MenezesKK,MagalhãesLC.Effectsofearlyinterventionsfocusedon thefamilyinthedevelopmentofchildrenbornpretermand/oratsocialrisk:ameta-analysis.JPediatr(RioJ).2020;96:20---38.

夽夽StudyconductedatUniversidadeFederaldeMinasGerais(UFMG),BeloHorizonte,MG,Brazil.

∗Correspondingauthor.

E-mail:rcfﬁsio2016@gmail.com(R.C.Ferreira).

https://doi.org/10.1016/j.jped.2019.05.002

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Earlyinterventionfocusedonthefamily:ameta-analysis 21 preterminfants.Therewasnobeneﬁtoftheinterventioninthecognitive,motor,andlanguage outcomesofchildrenwiththesocialriskfactorassociatedtobiologicalrisk.

Conclusion: Earlyinterventionfocusedonthefamilyhasapositiveeffectonthecognitionof preterm infants.The effectonmotordevelopment waslower,possiblyduetotheemphasis oninterventionsinfamily---childinteraction.Theeffectofinterventionsonthedevelopment ofchildrenatsocialriskandonthelanguagedomainwasinconclusive,duetothescarcityof studiesinthearea.

4.0/).

PALAVRAS-CHAVE Intervenc¸ãoprecoce (educac¸ão);

Pais;

Desenvolvimento infantil;

Bebê;

Recém-nascido prematuro;

Fatoresderisco

Efeitosdaintervenc¸ãoprecocecomfoconafamílianodesenvolvimentodecrianc¸as nascidasprematurase/ouemriscosocial:metanálise

Resumo

Objetivo: Verificarseaintervençãoprecocecomfoconafamíliamelhoraodesenvolvimento cognitivo, motor e a linguagem de crianças nascidas prematuras e/ou em risco social nos primeirostrêsanosdevida.

Fontesdedados: Metanálise de ensaios clínicos publicados entre 2008 a 2018, nas bases de dados CINAHL, Medline ---Pubmed, Medline ---BVS, Lilacs ---BVS, IBECS --- BVS, PEDro e Cochrane/Reviews.Foramincluídosestudosexperimentaisdeintervençãoprecocecomfoco na famíliacujopúblico-alvo eram prematurose/ou crianças em risco social comavaliação dodesenvolvimentocognitivoe/oumotore/oulinguagematéostrêsanos.Osartigosforam pontuadospelaEscalaPEDro.

Síntesedosdados: Dototalde3378artigos,12estudosforamincluídos.Aintervenc¸ãoprecoce comfoconafamíliacontribuiuparaodesenvolvimentodosdomínioscognic¸ão(DMP=0,48;95%

IC:0,34---0,61)emotor(DMP=0,76;95%IC:0,55---0,96)deprematuros.Nacognição,amelhora do desempenhofoi observadaaos12,24 e36 meses,enquanto nodomínio motor,oefeito foiobservadoapenasaos12mesesnosprematuros.Nãohouvebenefíciodaintervençãonos desfechos cognitivo, motor elinguagem de crianças comfator de riscosocial associado ao biológico.

Conclusão: Intervençãocomfoconafamíliatemefeitopositivosobreacogniçãodecrianças prematuras.Oefeitonodesenvolvimentomotorfoimenor,possivelmentedevidoàênfasedas intervençõesnainteraçãofamília-criança.Oefeitodasintervençõessobreodesenvolvimento decriançasemriscosocialenodomíniodalinguagemforaminconclusivos,devidoàescassez deestudosnaárea.

0/).

Introduction

Early childhood is a critical period for brain maturation, being crucial for cognitive, socio emotional, and physical development. It is at this stage that neural circuits areformed or strengthenedthroughinteractions withthe environment.^1---3Estimatesindicatethatinlow-andmiddle- incomecountries,morethan200million(43%)ofchildrenup to5yearsofagefailtoreachtheirdevelopmentpotential due to exposure to biological, psychosocial, and environ- mental risks,such asinadequatestimulation in the home environment.^4,5Inpreschool,childrenexposedtothesefac- torsmayshowahigherfrequencyofemotionaldifficulties, agitated behavior, deficiencies in executive functions and self-control,learning disabilities,Attention Deficit Hyper- activityDisorder(ADHD),andmentalhealthproblems.^2,6,7

In low- and middle-income countries, social and biological risks, represented by prematurity, often occur

concomitantly.^8,9 Prematurity is associatedwithincreased neonatal morbidity that generates risk for sensory and attention deﬁcits, learning disabilities, ADHD and autism symptoms,motororglobaldevelopmentaldelay,andCere- bralPalsy(CP),whichlimitssocialparticipationandreduces thequalityoflifeofthesechildren.^10---15

Investments in early childhood can reduce the effects ofsocialandbiologicalrisksandbringbeneﬁtsthroughout life.Earlyinterventionreferstopreventiveprogramsimple- mentedshortly after birth and upto 3years of age⁸ and consists of multidisciplinary clinical-therapeutic services providedtochildrenatriskandtheirfamiliesforthepur- poseofpromotingchildhealthandwell-being,stimulating emergingskills, minimizing developmentdelays, reducing existingdisabilities, preventing loss of functionality, con- tributingtothe structuringof themother---baby bondand thereceptionofthesechildrenbythefamily,andpromoting adaptiveparentingandoverallfamilyfunctioning.^16,17

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22 FerreiraRCetal.

Earlyinterventionfocusedonthefamilyaimstosupport familydynamicsinthedomestic environment.¹⁸ Thistype of approach has been recommended due to the possibil- ityofinﬂuencingthecareandstimulioffereddailybythe familyand,consequently,havingapositive impactonthe child’sdevelopment.^18---22Itsmaincomponentsarepsychoso- cialsupportandparentaleducation.²³Psychosocialsupport toparentsisaimedatreducingstress,anxiety,anddepres- sivesymptoms,aswellasincreasingmaternalself-efﬁcacy, sensitivity,andthe mother’sabilitytorespondin interactions with her child, which has a positive effect on the child’senvironmentandcontributestoimprovingthedevel- opmentaloutcome.²³ Parental education aimstoincrease the parents’ capacity, knowledge, and ability tocare for theirbaby.²³

Although it seems intuitive that improving the parent---child relationship results in gains for the baby’s development, the effectiveness of early intervention focused on the family programs has yet to be fully established. The planning of scientific evidence-based interventions allows the prioritization of problems, the estimationofrisksandbenefitsoftheintervention,andthe monitoring and evaluation of the results.²⁴ The synthesis ofscientificevidencegeneratedbysystematicreviewsand meta-analyses, together with the experience of health professionals and patient preferences, can also support decision-makinginclinicalpractice.²⁵Inthissense,thepur- poseof thismeta-analysiswastoevaluate andsynthesize theevidence available inthe literature about theeffects ofearlyinterventionfocusedonthefamilyprogramsonthe cognitive, motor, and language development of preterm childrenand/or those at socialrisk in the first3 yearsof life.

Methods

TheprotocolforthisreviewwasregisteredinPROSPERO:the International Prospective Register of Systematic Reviews (CRD 42018082059) (available at http://www.crd.york.

ac.uk/PROSPERO/displayrecord.php?ID=CRD42018082059).

ThereviewfollowedtherecommendationsoftheCochrane Library²⁶ and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).²⁷ Two independent authors carried out the literature search in the CINAHL, MEDLINE---PubMed,MEDLINE---BVS,LILACS---BVS,IBECS--- BVS,PEDro,andCochraneReviewdatabasesforstudiespub- lishedin thelast10years(January2008---August 2018),in threelanguages(Portuguese,English,andSpanish).Asearch wasalsocarriedoutinthereferencesectionsofthestudies foundinthedatabases.Threesearchstrategieswereused, usingpreviously chosen terms after consulting theHealth SciencesDescriptors(DeCS),includingthefollowingterms:

(1) Infant or Infant, Premature or Premature or Infant, NewbornandChildDevelopmentorLanguageDevelopment or Child Language or Psychomotor Performance or Motor Skills or Cognition and Early Intervention (Education) or EarlyIntervention;(2) InfantorInfant,Premature orPre- matureorInfant,NewbornandDevelopmental Disabilities or Delay Development and Early Intervention (Education) or Early Intervention; (3) Infant or Infant, Premature or PrematureorInfant,NewbornandMotorSkillsDisordersor

CognitionDisordersorMovementDisordersorLanguageand EarlyIntervention(Education)orEarlyIntervention.

Selectioncriteria

Thefollowingwereincluded:(1)Experimentalstudies,such asrandomized,quasi-experimental,andsingle-caseexper- imental trials; (2) Studies whose target audiences were prematurechildren withgestationalage<37weeks,with- outneuromotorabnormalitiesorcongenitalabnormalities, and/orchildrenatsocialrisk;(3)Studiesonearlyinterven- tionfocusedonthefamilyprogramsthatincluded atleast one of the following two main components: psychosocial supporttoparents,which couldbepsychological counsel- ingorsocialsupportand/orparentaleducation,whichcould includeinformationonchilddevelopment,demonstrations of childbehaviorwithdiscussion,or parentalinvolvement in parent---babyinteractionactivities, withfeedback from theprofessional;(4)Earlyinterventionfocusedonthefam- ily programs,performed during home visits and/or during the outpatient consultation, before and/or after hospital discharge,withindividualand/or groupcare;(5)Those in whichmotorand/orlanguageand/orcognitiondevelopment were evaluatedup tothe third year of lifethrough standardized tests. Systematic reviews and/or meta-analyses, longitudinal,cross-sectional,casereports,cohort,andcase- controlstudieswereexcluded.Allstudieswereevaluatedby thePEDroscaleofthePhysiotherapyEvidenceDatabase,²⁸ excludingthosewithascore≤5.

Validityandbiasriskassessment

Eligibility and quality evaluation of the studies were conductedbytwoindependentevaluators,whoinitiallyana- lyzed titles and abstracts to obtain potentially relevant studies.Thosethatmettheeligibilitycriteriaofthisreview wereread infulland scoredaccording tothe PEDroscale criteria²⁸toassessthemethodologicalquality.

The PEDro scale²⁸ is based on the Delphi list and has 11 items, and the item ‘‘speciﬁcation of inclusion criteria’’ is not scored, whereas the other items of the scale are:subjectinclusioncriteria;randomallocation;allocation concealment; similarityof thegroups inthe initialphase;

masking ofthesubjects,thetherapist,andtheevaluator;

measurementof atleastonekeyresult;analysisof inten- tiontotreat;resultsofthestatisticalcomparisonbetween groups andreportingof measuresofvariability;andaccu- racyofatleastoneoutcome.Eachitemreceivesonepoint whenitmeetstheresponsecriteria,foratotaloftenpoints.

Inthepresent study,aimingtoselectstudieswithgreater methodologicalaccuracy,acutoffscore>5wasused.

The risk of bias analysis of the included studies was performed by two reviewers, according to the Cochrane Handbook for Systematic Reviews of Intervention, taking intoaccountthegenerationofarandomizationsequence, allocation concealment, masking, incomplete data, and othersourcesofbias.Eachitemwasclassiﬁedas‘‘lowrisk ofbias’’,‘‘highriskofbias’’or‘‘unknownriskofbias’’.²⁹

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Earlyinterventionfocusedonthefamily:ameta-analysis 23 Dataanalysis

A table with the following variables was created to ana- lyzethedata:studyidentiﬁcation(titleandauthors),year of publication, country where the study was performed, samplesizeandcharacteristics,children’sage,earlyinter- ventioncharacteristics(descriptionoftheintervention,age at the intervention, individual- or group-based, carried out at the hospital or at home, before or after hospital discharge, andnumber ofsessions), outcomes, evaluation tools,results/conclusionsandPEDroscores.²⁸

To obtain the analysis of the combined estimate of the intervention effects, post-intervention scores were extractedandanalyzedusingthefixed-effectmodel.Inthe case of statistically significant heterogeneity (I²>40%), a randomeffectsmodel wasapplied.The pooleddatafrom alloutcomeswererecordedastheStandardizedMeanDif- ference(SMD)andtheirrespective95%ConfidenceIntervals (95% CI). The analyses were performed using the Com- prehensiveMeta-Analysissoftware³⁰(version3.0;Biostat--- Englewood, NewJersey,USA).The criticalvalue toreject thenullhypothesiswassetatalevelof0.05(two-tailed).

Results

Flowchartofthereviewstudies

Theelectronicsearchidentiﬁed3378studiesinthediffer- entdatabases,whosetitlesand/orabstractswereanalyzed.

Ofthese,3345wereexcludedandthe33potentiallyeligi- blestudieshadtheirtextsanalyzed.Basedonthereading ofthefulltexts,13studieswereselectedandscoredusing thePEDroscale.²⁸ Ofthese,threewereexcludedbecause theyshowedscores≤5,andtherefore,tenwereselected.

Duringthemanualsearchofthereferencesofthe10stud- iesselectedfromthedatabase,another10werefound,but only two studies were related to the topic and received scores>5accordingtothePEDroscale.Therefore,12stud- ieswereincludedinthequalitativeanalysisand10studies wereincludedinthequantitativeanalysis(meta-analysis).

Fig.1depictsthereviewﬂowchart(adaptedfromPRISMA).

Characteristicsoftheincludedstudies

The 12 studies selected for the review included 2559 participants (intervention=1305 and control=1254) and investigatedseveninterventionmodalitiestopromotebet- ter child development; they had guidelines for parents andparentaleducationasa commoncomponent.Allclin- icaltrialscomparedtheinterventiontothecontrolgroup, which received the usual care consisting of standard ser- vice care without the intervention, including referral to anearlyintervention/physicaltherapyserviceifthehealth team considered it necessary20,21,31---33; clinical care, mas- sage guided by a physical therapist, and follow-up after discharge^34,35; usual care with child-centered interventions and visits to the neonatal clinic³⁶; usual care that includedthekangaroomothercarepositionandmethod³⁷; homevisitsbasedontheWorldHealthOrganization(WHO) curriculum^5,38andinonlyonestudy,thestandardcarewas

notspeciﬁed.³⁹ Thecharacteristicsoftheinterventionand thecontrolfollow-up inthe reviewedstudies aresumma- rizedinTable1.

Theoverallcharacteristics andoutcomesofthestudies are summarized in Table 2. Most of the selected studies werecarriedoutinhigh-incomecountries:theNetherlands (three), Norway(two), Australia (two) and Canada(one).

Theother studiesarefromlow- andmiddle-incomecountries:India,Pakistan,andZambiatogetherhadtwostudies published,andTaiwan, Jamaica, Antigua,and SaintLucia published one study each. Most of them --- 9 of the 12 included--- reportedpositiveeffectsofcognitioninterven- tion.Regardingthemotoroutcome,5ofthe11studiesthat evaluatedthisoutcomefoundpositiveeffects.However,in thefourstudiesthatevaluatedlanguage,noeffectsofthe interventionwereobserved.

All studies wererandomized clinical trials,with PEDro scalescoresranging from6to8points(meanof6 points) (Supplementary Material 1 presents the score details).

Regardingtherisk ofbias(Fig.2),theabsenceof subject allocationconcealment wasobserved for theintervention andthe controlgroups in six studies, absenceof masking oftheparticipantsandoftheprofessionalwhoperformed theclinical trial intervention wasobserved in all studies, aswell asdifferencesinthesample characteristics inthe interventionandcontrolgroupsatbaselineintwostudies.

Participants

Most reviewed studies had a target audience of preterm children, withthree evaluating children born withgestationalage<32weeksand/orweighinglessthan1500grams (g)^20,32,33; one evaluating children born with age gestational age<32 weeks and/or birth weight between 500g and 1250g³⁷; and one whose sample had a gestational age<30 weeks.²¹ The other studiesthat assessedpreterm infantshadasinclusioncriteriaonlybirthweight<2000g^34,35 and one had participants with birth weight<1500g.³⁶ All studiesthat assessedpreterm infants hadexclusion criteria for congenital abnormalities. The other studies (four) assessedchildren considered tobe at socioeconomicrisk, butonlyonestudyexclusivelyassessedsocialrisk,excluding preterm children.³⁹ In the others, children with and without neonatal asphyxia were included, both at-term andpreterminfants, excluding preterminfants withbirth weight<1500g^5,38andonestudyassessedprematureinfants withgestationalage<30weeks,whowereclassiﬁedashav- inghighorlowsocialrisk.³¹

Assessmentofcognitive,motorandlanguage development

Thecognitiveoutcomewasassessedinallofthereviewed studies, whereas 11 studies assessed the motor development,butonlyfourstudiesincluded languageassessment.

TheBayleyScalesofInfantDevelopment2ndEdition(Bayley II)wasthetestusedforoutcomeevaluationin moststud- ies(eightstudies).5,20,32---35,37,38 The other studies usedthe BayleyScalesofInfantDevelopment3rdEdition(BayleyIII) (three studies)^21,31,36 andthe GrifﬁthMentalDevelopment

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24 FerreiraRCetal.

IdentificationSelectionEligibilityInclusion

Records identified in the database search (n = 3,378)

Excluded and/or duplicate records (n = 3,345)

Full texts of articles assessed for eligibility (n = 33)

Texts excluded because they were not related to the topic (n = 20)

Selected studies rated using the PEDro Scale (n = 13)

Studies with scores PEDro scale (n = 10)

Excluded studies with a score ≤ 5 by the PEDro scale

(n = 3)

Studies found during the manual search in the references of the

selected studies and with score > 5 by the PEDro scale (n = 2) Studies included in the qualitative

synthesis (n = 12)

Studies included in the quantitative synthesis of the meta-analysis

(n = 10)

Figure1 Studyﬂowchart.

AdaptedfromPreferredReportingItemsforSystematicReviewsandMeta-Analyses---PRISMA.

ScalesandtheMacArthur-BatesShortFormoftheCommu- nicativeDevelopmentInventory(CDI)(onestudy).³⁹

The age at the evaluation of child development var- iedgreatly,and inone-third ofthestudies theevaluation wasperformed at 24months(fourstudies).Intheothers, theevaluations wereperformed from 12to 36 monthsof age (one study); at 12, 24 and 36 months (two studies);

at 18 months (one study); and at 6 months (one study).

Inthree studies, alongitudinal evaluation wasperformed for a longer period, in two studies up toﬁve and a half yearsandin onestudy up to8years, butasthe focusof themeta-analysiswasinterventionsintheﬁrst 3yearsof

life,onlytheresultsrelatedtothisagegroupwereconsid- ered.

Characteristicsoftheearlyinterventionfocused onthefamilyprograms

Table 1 shows the characteristics of early interventions focused on the family. In most studies, the interventions wereindividual,withanumberofsessionsrangingfrom5to 13,mostlyperformedafterhospitaldischargeandduringthe child’sﬁrst12monthsoflife20,21,31---36 andallinterventions

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Earlyinterventionfocusedonthefamily:ameta-analysis25 Table1 Characteristicsofinterventionprogramsandproceduresperformedinthecontrolgroupoftheincludedstudies.

Author/year Descriptionofintervention Interventioncomponent Interventiontype Placeofintervention N^◦ofsessions andageatthe intervention

Control

Parental education

Supportto parents

Individual Group Hospitaloutpatient clinic

Home

Spittleetal.³¹ (2018)

VIBeSPlus--- twocomponents:

(1)strategiestopromote enrichedenvironment,positive play,generaldevelopmental milestones,feeding,sleep,and well-beingofparents,(2) speciﬁccontentthatwas targetedtothebabyand familybasedongoalsand/or concernsidentiﬁedbythe parents.

Yes Yes Yes --- --- Yes N^◦ofsessions:

9sessionsafter discharge.Age:

ﬁrst12months

Controland interventiongroup receivedstandardized care:includedaccess toachildhealth nurseandearly interventionservice, ifitwasconsidered appropriatebythe child’shealthteam.

VanHusetal.³² (2016)

IBAIP--- offersupporttothe child’sregulatorycompetence andmultipledevelopment functionsthroughchild-parent interaction.Basedonthe synchronous-activemodelof theneonate’sbehavioral organization,guidedbythe InfantBehavioralAssessment, asystematicobservationtool fortherecordingand interpretationofthebaby’s communicationbehaviors.

Yes --- Yes --- Yes Yes N^◦ofsessions:

7to9sessions (1before hospital dischargeand6 to8sessions duringhome visits).Age:

ﬁrst6months

Usualcare:including referraltoregular pediatricphysical therapyifdeemed necessarybythe pediatrician.

Changetal.³⁹ (2015)

DevelopmentMedia International,London, UK-demonstrationusingﬁlms depictingthebehaviorsthat theinterventionshould stimulate,followedby discussionanddemonstration oftheviewedactivities.The motherspracticedthe activitieswiththeirchildren andwereencouragedto performthemathome.

Yes --- --- Yes Yes --- N^◦ofsessions:

5outpatient sessions performed after discharge.

Ages:3,6,9, 12,and18 months

Usualcare:not speciﬁedbythestudy

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26FerreiraRCetal.

Table1(Continued)

Control

Parental education

Supportto parents

Home

Wuetal.³⁶ (2014)

Itconsistedoftwointervention groupsinthesameprogram, whichwasdifferentiatedonly regardinglocation:onewas performedatthehospitaland theotherathome.

Interventioncenteredonthe child-parentdyadandclinical consultations.Priortohospital discharge,theintervention wasguidedbyprinciplesofthe synchronous-activeTheoryand family-centeredcare.After discharge,thetheoryof biosocialsystemswasused.

Yes Yes Yes --- Yes Yes N^◦ofsessions:

13sessions(5 sessionsbefore dischargeand8 sessionsafter discharge).

Ages:36,38, and40weeks before

dischargeand1 weekafter discharge,1,2, 4,6,9and12 monthsofage after

discharge.

Usualdevelopmental care,whichconsisted ofintra-hospital interventions centeredonthechild andconsultationat theneonatalclinic

Wallanderet al.⁵(2014)

PartnersforLearning---which encompassestheareasof cognition,ﬁneandgrossmotor, social,self-helpandlanguage skills.Parentsweretrainedto performactivitiesthatwere adequatetothechild’s developmentandpracticed theminthepresenceofthe professional,whogave feedback.Parentsreceived cardsdescribingactivitiesand wereencouragedtoapply activitiesduringtheroutine careofthechilduntilthenext homevisit.

Yes --- Yes --- --- Yes N^◦ofsessions:

72.Age:ﬁrst3 years.

Homevisits:WHO curriculum(2014) whichaddressed,for instance,breast feeding,nutrition, hygieneand vaccination.

Bannetal.³⁸ (2016)

PartnersforLearning---same characteristicsmentionedin thestudybyWallanderetal.⁵ (2014).

Yes --- Yes --- --- Yes N^◦ofsessions:

72sessions.

Age:ﬁrst3 years

Samecharacteristics asthestudyby Wallanderetal.⁵ (2014)

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Earlyinterventionfocusedonthefamily:ameta-analysis27

Table1(Continued)

Control

Parental education

Supportto parents

Home

Spittleetal.²¹ (2010)

VIBeSPlus--- same

characteristicsmentionedin thestudybySpittleetal.³¹ (2018)

Yes Yes Yes --- --- Yes N^◦ofsessions:

9Sessionsafter discharge.Age:

ﬁrst12months

Samecharacteristics asthestudyby Spittleetal.³¹(2018) Koldewijn

etal.³³(2010)

IBAIP--- samecharacteristics mentionedinthestudybyVan Husetal.³²(2016)

7to9sessions (1before dischargeand6 to8sessionsat home).Age:

ﬁrst6months

Samecharacteristics asthestudybyVan Husetal.³²(2016)

Nordhov etal.³⁴(2010)

Mother---InfantTransaction Program--- modiﬁedversion:it addressedaspectssuchasthe child’sreﬂexes,

self-regulation,signsof distressandthechild’s predominantstatesand adjustmenttothehome environment,parent---child interactions,howtoguideand stimulatethechild,and discussionandevaluationof theinterventionprogram.

11sessions(7 sessionsbefore dischargeand4 homevisits).

Ages:3,15,30, and90days afterdischarge

Usualcarefor discharge:clinical examination,infant massagetraining performedby physicaltherapist.

Bothgroupshad accesstofollow-up afterdischarge

Koldewijn etal.²⁰(2009)

IBAIP---samecharacteristics mentionedinthestudybyVan Husetal.³²(2016).

7to9sessions (1before dischargeand6 to8sessionsat home).Age:

ﬁrst6months

Samecharacteristics asthestudybyVan Husetal.³²(2016)

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28FerreiraRCetal.

Table1(Continued)

Control

Parental education

Supportto parents

Home

Petersetal.³⁷ (2009)

NIDCAP---Characterizedby observationofbaby’sbehavior.

Encouragesparentalled involvementguidedbythe babyandrequiresparentsto respondtoindividualinfant behaviors,bemoreﬂexiblein caringandmodifythe environmentinaccordance withobservedbehaviors.

Yes --- Yes --- Yes --- N^◦ofsessions:

7sessions (carriedoutin theICU).Age:

notinformed

Usualcarethat includedpositioning, kangaroomethod,but withoutintervention andbehavioral observation

Kaaresen etal.³⁵(2008)

Mother---InfantTransaction Program-modiﬁedversion---the samecharacteristics

mentionedinthestudyby Nordhovetal.³⁴(2010)

11sessions(7 sessionsbefore dischargeand4 homevisits).

Ages:3,15,30 and90days afterdischarge

Thesame characteristics mentionedinthe studybyNordhov etal.³⁴(2010)

VIBeSPlus,VictorianInfantBrainStudies;IBAIP,InfantBehavioralAssessmentandInterventionProgram;NIDCAP,NewbornIndividualizedDevelopmentalCareandAssessmentProgram;

BayleyII,TheBayleyScalesofInfantDevelopment,2ndEdition;BayleyIII,TheBayleyScalesofInfantDevelopment,3rdEdition.

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Earlyinterventionfocusedonthefamily:ameta-analysis29 Table2 Generalcharacteristicsandoutcomesofincludedstudies.

Author/year Participants Countryoforigin ofthesample

Intervention/evaluation tool/ageatevaluation

Positiveeffectoftheinterventionon development

Additionalinformationon theeffect

Cognition Motor Language

Spittleetal.³¹ (2018)

PMTGA<30weeks classiﬁedashighor lowsocialrisk.

n=120(intervention groupn=61,control groupn=59).

Australia VIBeSPlus/BayleyIII;

Age:24months

Yes Noeffect Noeffect Highermeancognitivescore intheinterventiongroup (101.8;SD=11.0)ofthe childrenatsocialriskwhen comparedtothecontrol group(92.2;SD=12.5);

p=0.006at24monthsof age

VanHusetal.³² (2016)

PMTGA<32weeks and/orBW<1500g;

TheNetherlands IBAIP/BayleyII;Ages:6, 12,and24months

Yes Yes Notevaluated Positivelongitudinaleffect ofinterventiononmotor development(SD=0.4;

p=0.006),butnoton cognition(p=0.063).

Childrenwith

bronchopulmonarydysplasia hadasigniﬁcant

longitudinaleffecton cognitive(SD=0.7p=0.019) andmotoroutcomes (SD=0.9,p=0.026).

Changetal.³⁹ (2015)

Childrenatsocialrisk (bornfull-term):

Jamaica,Antigua, andSantaLucia (Caribbean)

DevelopmentMedia International,London, UnitedKingdom/Grifﬁth MentalDevelopment Scalesand

MacArthur-BatesShort Formofthe

Communicative DevelopmentInventory (CDI).Age:19.7months.

Yes Noeffect Noeffect Signiﬁcanteffecton

cognition(3.09points,95%

CI:1.31---4.87,effect size=0.3),butnoton languageormotor development.

Wuetal.³⁶ (2014)

PMTGA<37wks.and BW<1500g:n=178 (outpatient interventiongroup n=57,home interventiongroup n=63,controlgroup n=58).

Taiwan Synchronous-active theoryand family-centered care/BayleyIII.

Ageatassessment:24 months.

Yes Yes Noeffect Outpatientintervention

grouphadahigher cognitionscorecompared tothecontrolgroup (difference=4.4,95%CI:

0.8to−7.9)andalower rateofmotordevelopment delay(OR=0.29,95%CI:

0.08---0.99).

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30FerreiraRCetal.

Table2(Continued)

Additionalinformation ontheeffect

Wallander etal.⁵(2014)

Childrenat socioeconomic disadvantage(preterm andfullterm)n=407 (interventiongroup n=204,controlgroup n=203).

Ruralareasof India,Pakistan, andZambia

Partnersfor

Learning/BayleyII.Age atevaluation:12,24and 36months.

Yes Yes Notevaluated Consideringthe

interactionbetweenage andintervention,the childreninthe interventiongroup showedabetter trajectoryinthe developmentof cognitioninthethree evaluations(12,24,and 36months).At36 months,thechildrenin theinterventiongroup showedasigniﬁcantly highermotorscore comparedtothecontrol group.

Bannetal.³⁸ (2016)

Childrenat socioeconomic disadvantage(preterm andfullterm)n=293 (interventiongroup n=146,controlgroup n=147).

Ruralareasof India,Pakistan, andZambia

Partnersfor

Learning/BayleyII.Age atevaluation:12,24and 36months

Yes Notevaluated Notevaluated Intheeconomically disadvantagedchildren, theinterventiongroup showedahighermental scorethanthecontrol groupat36monthsof age(p=0.001).

Spittleetal.²¹ (2010)

PMTGA<30wks.:n=120 (interventiongroup n=61,controlgroup n=59).

Australia VIBeSPlus/BayleyIII.

Ageatevaluation:24 months.

Noeffect Noeffect Noeffect Therewasno

statisticallysigniﬁcant differenceregardingthe cognition,language,and motorscores(p=0.20, p=0.67,p=0.66, respectively).

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Earlyinterventionfocusedonthefamily:ameta-analysis31 Table2(Continued)

Additionalinformationon theeffect

Koldewijn etal.³³(2010)

PMTGA<32weeks and/orBW<1500g:

TheNetherlands IBAIP/BayleyII.Ageat evaluation:24months

Yes Yes Notevaluated Afteradjustmentfor

perinatalvariables,there wasaneffectof6.4 (standarderror=2.4)onthe motordevelopmentindex favorabletothe

interventionchildren.After theposthocanalysis,there wasbettermental

developmentafterthe interventioninthe subgroupsofchildrenwith bronchopulmonarydysplasia associatedwithsocialand biologicalriskfactors.

Nordhov etal.³⁴(2010)

PMTBW<2000g n=146(intervention groupn=72,control groupn=74).

Norway Mother---Infant Transaction Program-modiﬁed version/BayleyII.Ageat evaluation:3years.

Noeffect Noeffect Notevaluated At3yearsofage,inthe analysisafteradjustment formaternaleducation,no signiﬁcantdifferencewas foundbetweenthe interventionandcontrol groupsregardingthemental developmentindexscoreof 4.5points(95%CI:−0.3to 9.3)

Koldewijn etal.²⁰(2009)

PMTGA<32weeks and/orBW<1500g, n=176(intervention groupn=86,control group,n=90).

TheNetherlands IBAIP/BayleyII.Ageat evaluation:6months

Yes Yes Notevaluated Afteranalysiswitha

multivariateregression model,themeanMDIscore was106(SD=2.12)forthe interventiongroupand99 (SD=2.18)forthecontrol group(p=0.02).Inthe motorscore,themeanPDI scorewas98(SD=1.63)in theinterventiongroupand 92(SD=1.66)inthecontrol group(p=0.008).

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32FerreiraRCetal.

Table2(Continued)

Additionalinformation ontheeffect

Petersetal.³⁷ (2009)

PMTGA≤32weeks,BW between500and1250g;

n=120(intervention group=60,control group=60).

Canada NIDCAP/BayleyII.Ageat evaluation:18months.

Yes Noeffect Notevaluated Lowerfrequencyof cognitiondelay (intervention:10%, control:30%;OR=0.25;

95%CI:0.08---0.82, p=0.017).

Kaaresen etal.³⁵(2008)

PMTBW<2000g:n=146 (interventiongroup n=72,controlgroup n=74).

Norway Mother---Infant Transaction Program-modiﬁed version/BayleyII.Ageat evaluation:24months.

Noeffect Noeffect Notevaluated Mentaldevelopment index:Difference betweenthemeansof theinterventionand controlgroupsequalto 0.7(95%CI:−4.3to6.0) (p=0.74).

Motordevelopment index:Difference betweenthemeansof theinterventionand controlgroupsequalto 1.2(95%CI:−4.3to6.8) (p=0.66).

PMT,prematurity;BW,birthweight;GA,gestationalage;VIBeSPlus,VictorianInfantBrainStudies;IBAIP,InfantBehavioralAssessmentandInterventionProgram;MDI,MentalDevelopmental Index;PDI,PsychomotorDevelopmentalIndex;NIDCAP,NewbornIndividualizedDevelopmentalCareandAssessmentProgram;BayleyII,BayleyScalesofInfantDevelopment,2ndEdition;

BayleyIII,BayleyScalesofInfantDevelopment,3rdEdition.

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Earlyinterventionfocusedonthefamily:ameta-analysis 33

Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias) Other bias

Low risk of bias Unclear risk of bias High risk of bias

0% 25% 50% 75% 100%

Random sequence generation (selection bias) Allocation concealment (selection

Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias) Other bias

BANN et al, 2016

CHANG et al, 2015

KAARENSEN et al, 2008

KOLDEWIJN et al, 2009

KOLDEWIJN et al, 2010

NORDHOV et al, 2010

PETERS et al, 2009

SPITTLE et al, 2010

SPITTLE et al, 2018

VAN HUS et al, 2016

WALLANDER et al, 2014

WU et al, 2014

A

B

Figure2 Judgmentoftheauthorsofthemeta-analysisforeachbiasriskitemfortheincludedstudies:(A)biasrisksummaryand (B)biasriskgraph.

involvedcomponentsofguidelinesforparentsandparental educationtostimulatechilddevelopment,mainlythrough thesynchronous-activetheory.^20,32---37 Althoughthepurpose ofthisreviewwastoaddress interventionsfocusedonthe family in most studies, the family was restricted to the involvement of mothers and fathers, with the exception ofthestudybyChangetal.,³⁹ inwhichearly intervention involvedonlythemothers.

The InfantBehavioralAssessmentandInterventionPro- gram (IBAIP) was investigated in three studies,^20,32,33 the Mother---Infant Transaction Program-modiﬁed version in two,^34,35 onestudyusedtheNewbornIndividualizedDevel- opmental Care and Assessment Program (NIDCAP),³⁷ two studies used the Victorian Infant Brain Studies (VIBeS Plus)^21,31 andtwostudies hadtheirinterventionsbasedon the Partners for Learning curriculum.^5,38 The other two addressed educational guidelinesfor parents through ﬁlm viewing,discussionsandsupporttoparents.^36,39

Effectsofearlyinterventionfocusedonthefamily oncognition

The effectsof theearly interventionfocused onthefam- ilyonthecognitionofpretermchildrenwereevaluatedin

eightclinical trials.20,21,32---37 Theinterventionsandrespec- tiveassessment tools usedin the studies were:IBAIPand BayleyII^20,32,33;Mother---InfantTransactionProgram---mod- iﬁedversionandBayleyII^34,35;VIBeSPlusteamandBayley III²¹andNIDCAPandBayleyII.³⁷Inoneofthestudies,³⁶two groupsunderwent thesame earlyintervention focused on the family,one at home and the other at the outpatient clinic,usingtheBayleyIIIevaluationtool.Alltheinterven- tions showed previously mentioned characteristics, based mainlyonthesynchronous-activetheory.^20,32---37Thecontrol groupsreceivedtheusualservicecare,butwithouttheearly interventionfocusedonthefamily.

Theanalysisoftheinterventioneffectsonthecognition of preterm infants was performed by grouping data from theeightstudies(n=1238participants; intervention=643, control=595). In the overall result,children receiving an early intervention focused on the familyhad a standard- izedmeanof cognitivescores of 0.48(95% CI:0.34---0.61, p-value<0.001, I²=39%), higher than the children who receivedtheusualservice care.In twostudies,theintervention effects oncognition were evaluated at 6 months ofage^20,32 andtherewasnosigniﬁcantchangeincognition (SMD=1.83,95%CI:−1.08to4.74,p=0.21,I²=39%).

In the study in which the evaluation was performed at 12 months, 32 children who received the intervention

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34 FerreiraRCetal.

Group by Comparison

Study name

12,00 12,00 18,00

18,00 24,00 24,00 24,00 24,00

24,00 24,00

36,00 36,00 6,00 6,00 6,00

Overall

VAN HUS et al., 2016 b

PETERS et al, 2009

KAARENSEN et al, 2008 KOLDEWIJN et al, 2010 SPITTLE et al, 2018 VAN HUS et al., 2016 c

WU et al, 2014

NORDHOV et al, 2010

KOLDEWIJN et al, 2009 encontrado nas ref) VAN HUS et al., 2016 a

12,000

18,000

24,000 24,000 24,000 24,000

24,000

36,000

6,000 6,000

Comparison Statistics for each study

Std diff in means

Standard error

Lower limit

Upper limit

Variance Z-Value p-Value

0,864 0,164 0,027 0,027 0,040 0,040

0,000 0,021 0,006 0,025 0,000 0,009 0,030 0,000 0,071

0,071 0,225 -0,013 0,098 -0,099 0,429 -0,117 -0,078 -0,078

0,543 1,186 0.707 0.707

0.568 0.991 0.636 0.721

0.698 0.582 0.756

0,756 2,389 0,018 0,023 0.052 0.648 0,303 0,021 0,068 2,880 3,766 14,082 0,000

0,543 1,186 5,271 5,271 1,571 1,571 1,281 4,948 1,429 2,583 1,891 4,369 2,339

0,000 0,000 0,116

0,116

0,200 0,000 0,163 0,010 0,069

0,000 0,018 0,164

0,200 0,200 0,172 0,143 0,187

0,159

0,181 0,094 0,175 0,175 0,152 0,263 1,486

0,089 0,005 0,347 0,618 6,976 0,000

-4.00 -2.00

Control

0,00 2,00 4,00

2,209 -1,082 4,744 1,232 0,218 0,864

0,315 0,315 0,230 0,710 0,288 0,408 0,343

0,409 0,414

0,414 0,360 3,322 1,831 0,482

Std diff in means and 95% CI

Experimental

Figure3 Standardizedmeandifferenceand95%ConﬁdenceIntervaloftheeffectsofinterventiononthecognitiondomainof childrenbornpretermbyage.

showed a standardized mean of 0.86 (95% CI: 0.54---1.18, p<0.001, I²=39%) higher than the control group. In the studywithevaluationat18months,³⁷ therewasnosigniﬁ- cantchangeincognition(SMD=0.31,95%CI:−0.07to0.7, p=0.11,I²=39%).Inﬁvestudiestheevaluationwascarried out at 24 months31---33,35,36 and the children whoreceived theinterventionshowedastandardizedmeanofcognitive scoresof0.4(95%CI:0.22---0.59;p<0.001;I²=39%),higher thanthechildreninthecontrolgroup. Inasinglestudy,³⁴ theevaluationwasperformedat 36monthsandtherewas an increase in the standardized mean of cognitive scores of0.41 (95%CI:0.22---0.59, p=0.018,I²=39%) inthe chil- drenfromtheinterventioncomparedtothecontrolgroup (Fig.3).

Ofthefourstudiesthatevaluatedcognitioninthesam- pleofchildrenconsideredtobeatsocialand/orbiological risk, twostudies performed home interventions based on thePartnersforLearningcurriculum^5,38 andtheeffectwas evaluatedbytheBayleyIIscale.Inanotherstudy,theinter- ventionwasperformedbytheVIBeSPlusteamandthetool wastheBayleyIIIscale.³¹

Inthe fourth clinicaltrial,³⁹ the interventionconsisted of showing short ﬁlms by health education consultants (Development Media International, London, United King- dom), followed by discussion groups about the ﬁlms and practical activities withchildren, with the mothers being encouragedtoperformtheseactivitiesathomewiththeir children.

ThecognitiveoutcomewasevaluatedusingtheGrifﬁth MentalDevelopmentScalesandtheMacArthur-Bates Short

FormoftheCDI.Regardingthecharacteristicsoftheinter- ventions,allhadacomponentthatpresentedguidelinesfor parents for the developmentof the children, which were performedafterhospitaldischarge,withvariationsrelated totheothercharacteristics.

Theanalysisoftheinterventioneffectsonthecognition ofchildrenatsocialand/orbiologicalriskwasperformedby poolingdatafromtwostudies^5,31(n=527participants;intervention=265,control=262).Itwasnotpossibletoinclude thestudy byBann etal.,³⁸ becausetheydidnothave the necessary data for the meta-analysis.Although the initial proposalwastoconsideronlychildrenatsocialrisk,thiswas notpossible,sinceonlyonestudywasidentiﬁed³⁹withthis typeofsample.Therefore,themeta-analysiswasperformed withthetwostudiesthatincludedchildrenatsocialandbio- logical (prematurity)risk:Wallanderetal.,⁵ whoincluded pretermandat-termchildrenwithhighsocialrisk,andSpit- tleetal.,³¹whosesampleofpreterminfantswasclassiﬁed ashighorlowsocialrisk.

In the overall result, the intervention focused on the family did not promote a signiﬁcant change in cognition (SMD=0.79, 95%CI: −0.31 to0.46, p=0.69,I²=1%) when compared tochildren from the control group.In the two studiesthatassessedcognitionofchildrenathighsocialrisk (SMD=0.38,95%CI:−0.32to1.08,p=0.29,I²=1%),there wasnosigniﬁcantdifferenceinthecognitionscores.Inthe studywhosesamplehadlowsocialrisk(SMD=−0.05,95%CI:

−0.52to0.41,p=0.82,I²=1%)therewasalsonosigniﬁcant difference in cognition (For the plot, see Supplementary Material2).

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Earlyinterventionfocusedonthefamily:ameta-analysis 35 Effectsofearlyinterventionfocusedonthefamily

onmotordevelopment

Theeightstudiesthatevaluatedcognitioninpreterminfants also evaluated the motor outcome, thus the characteris- ticsof thestudiesarethesame asthosereportedfor the cognitionoutcome.

The effectsof the intervention on themotor outcome in the preterm population were analyzed by pooling the data from the eight studies (n=1238 participants; intervention=643, control=595).20,21,32---37 Inthe overall result, children who received early intervention focused on the family had a standardized mean of motor development scoresof0.76(95%CI:0.55---0.96;p<0.001;I²=88%),higher thanthechildrenwhoreceivedroutinecareattheservice.

Similarlytocognition,intwostudiesthemotoroutcomewas evaluatedat 6months(SMD=2.54,95%CI:−1.72to6.81, p=0.24, I²=88%) and there was nosigniﬁcant change. In onlyonestudy,theevaluationwasperformedat12months, andthechildrenintheinterventiongrouphadastandard- ized mean of motor development scores of 2.08 (95% CI:

1.7---2.46; p<0.001; I²=88%), higher than the children in thecontrolgroup.Onestudyevaluatedthemotoroutcome at 18months(SMD=0.26,95% CI:−0.13to0.65, p=0.19, I²=88%),ﬁvestudiesat24months(SMD=0.83,95%CI:−0.08 to1.75,p=0.07,I²=88%)andonestudyat36monthsofage (SMD=0.06,95%CI:−0.27to0.4,p=0.71,I²=88%),show- ingnosigniﬁcantchangeinthemotordomainattheseage ranges(Fig.4).

Inthreeofthefourpreviouslydescribedstudiesregard- ingthecognitiveoutcome, motordevelopmentevaluation was also performed in children at social and/or biologi- calrisk.^5,31,39Theanalysisoftheeffectsofinterventionon motor development was performed by pooling data from twostudies(n=527participants:intervention=265andcon- trol=262).^5,31ThestudybyChangetal.³⁹wasexcludedand the studies by Wallander etal.⁵ and Spittleet al.³¹ were

includedintheanalysis,aspreviouslyjustifiedinthecogni- tionoutcome.Intheoverallresult,therewasnosignificant difference regarding the motor development of children atsocialand/orbiologicalrisk whoreceivedtheinterven- tion(SMD=0.12, 95% CI: −0.05 to0.29, p=0.18, I²=0%), when compared to controls. In the two studies focused onthe motor developmentof children at high social risk (SMD=0.16, 95% CI: −0.03 to0.35, p=0.1, I²=0%), there wasnosignificantdifferencebetweenthecontrolandinter- ventiongroups, norinthe studythatincluded children at lowrisk(SMD=−0.1;95%CI:−0.57to0.36;p=0.65;I²=0%) (SupplementaryMaterial3presentstheplot).

Effectsofearlyinterventionfocusedonthefamily onlanguage

Twostudiesevaluatedtheeffectsoftheinterventiononthe languageof preterminfants.Oneofthe studiesisrelated to the intervention developed by the VIBeS Plus team, whoselanguageevaluationwasperformedusingtheBayley IIIscale.²¹ In theotherstudy,³⁶ twogroupsunderwentthe sameinterventionfocusedonthefamily,withadifference relatedonly totheintervention location--- at home or at theoutpatientclinic---andtheevaluationtoolwasalsoBay- leyIII.Regardingthecharacteristicsoftheinterventions,all hadguidelinesfortheparents’componentonthechildren’s development,andmost wereperformed individually,with thenumberofsessionsvaryingfrom9to13duringtheﬁrst 12monthsofthechild’slife,whichoccurredafterhospital discharge.Thecontrolgroupreceivedtheservice’sroutine care,butwithouttheintervention.

Theanalysisoftheinterventioneffectsonthelanguage ofthepreterm populationwasperformed bypoolingdata fromthetwostudies(n=298participants:intervention=181 andcontrol=117).^21,36 The analyzed studies didnot show anysigniﬁcant differenceinthe children’slanguagewhen comparingthosewhoreceivedtheintervention(SMD=0.02,

Group by Comparison

Study name Comparison Statistics for each study Std diff in means and 95% CI

Std diff in means

Standard error

Lower limit

Upper limit

Variance Z-Value p-Value

12,00 VAN HUS et al., 2016 b 12,000 2,081 0,195 0,038 1,700 2,462 10,697 0,000

12,00 2,081 0,195 0,038 1,700 2,462 10,697 0,000

18,00 PETERS et al, 2009 18,000 0,261 0,200 0,040 -0,131 0,652 1,304 0,192

18,00 0,261 0,200 0,040 -0,131 0,652 1,304 0,192

24,00 KAARENSEN et al, 2008 24,000 0,072 0,172 0,029 -0,265 0,408 0,418 0,676

24,00 KOLDEWIJN et al, 2010 24,000 1,010 0,150 0,023 0,716 1,305 6,723 0,000

24,00 SPITTLE et al, 2018 24,000 0,082 0,187 0,035 -0,284 0,448 0,439 0,661

24,00 VAN HUS et al., 2016 c 24,000 2,927 0,227 0,051 2,483 3,372 12,902 0,000

24,00 WU et al, 2014 24,000 0,112 0,180 0,032 -0,242 0,465 0,619 0,536

24,00 0,834 0,469 0,220 -0,085 1,752 1,778 0,075

36,00 NORDHOV et al, 2010 36,000 0,064 0,174 0,030 -0,277 0,405 0,368 0,713

36,00 0,064 0,174 0,030 -0,277 0,405 0,368 0,713

6,00 6,000 0,375 0,152 0,023 0,077 0,673 2,465 0,014

6,00 VAN HUS et al., 2016 a 6,000 4,731 0,298 0,089 4,147 5,315 15,873 0,000

6,00 2,546 2,178 4,744 -1,723 6,815 1,169 0,243

Overall 0,762 0,106 0,011 0,554 0,969 7,195 0,000

-4,00 -2,00 0,00 2,00 4,00

Control Experimental

Figure4 Standardizedmeandifferenceand95%ConﬁdenceIntervaloftheeffectsofinterventiononthemotorskillsofchildren bornpreterm,byage.

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36 FerreiraRCetal.

95% CI:−0.23 to0.27, p=0.87, I²=0) when compared to thosewhoreceivedtheusualservicecare.(Supplementary Material4presentstheplot).

Amongthepopulationatsocialand/orbiologicalrisk,in thestudyinwhichshortfilmscreatedbyDevelopmentMedia Internationalwereexhibited,³⁹thelanguagewasevaluated, onaverage,at 19months ofage, usingthelanguagesub- scale of the Griffith Mental Development Scales and the MacArthur-Bates Short Form of the CDI. In the study by Spittleetal.,³¹ languagewasevaluatedat 2yearsof age usingtheBayleyIIIscale.Bothstudiesshowednosignificant effectsonlanguage.Itwasnotpossibletocarryoutmeta- analysis,sinceChangetal.³⁹excludedpreterminfantsfrom thesampleandSpittleetal.³¹investigatedpreterminfants andtherefore,thesampleswereconsideredheterogeneous formeta-analysis.

Discussion

Thisreviewaimedtoverifytheeffectsofearlyintervention focusedonthefamilyoncognition,motordevelopment,and languageof childrenborn pretermand/or atsocial riskin theﬁrst3yearsoflife.Twelvestudieswereincluded,most withmoderatequality,5,20,21,31---33,36,38,39 which weremainly conductedinhigh-incomecountries.20,21,31---35,37Thesamples consistedmainlyofchildrenbornprematurely20,21,31---37and the only domain evaluated in all studies was the cognitive domain, with language being evaluated in only four studies.21,31,36,39 The programs based on the synchronous- activetheorywerethemostfrequentlyused.^20,32---37

Inthe overall result,early interventionfocused onthe family contributed to the development of cognition in preterm infants when compared to the usual care. This result is similar to that of the meta-analysis performed by Vanderveen et al.,²² which aimed to evaluate interventions involvingparents in thedevelopmentof preterm infants.Similarresultsregardingcognitionwerealsofound in a meta-analysis carried out by Spittle et al.,¹⁸ which observedimprovementinthecognitiveoutcomeinthegroup of children whoreceived intervention in the ﬁrst 3 years oflifecomparedtocontrols,althoughtheinterventionwas notexclusivelyfocusedonthefamily.Consideringtheage group,there wasa positive effect of intervention onthe cognitivedomainat12,24 and36monthsofage,butnot at6and18monthsofage.Vanderveenetal.²² alsofound positiveeffectsoftheinterventiononthecognitivedevel- opmentofpreterm infantsat ages12,24 and36months, butnotat6months.

Theeffectofearlyinterventionfocusedonthefamilyon thecognitionofpretermchildren,evidentatdifferentages, ispossiblyassociatedwiththetypes ofanalyzedinterven- tionprograms,which,forthemostpart,werebasedonthe principlesofthesynchronous-activetheory.^20,32---37According tothistheory,tomaintaintheorganizationofbehaviorand adaptivelyrespondtotheenvironment,thebabydependson theinteractionbetweenﬁvebasic subsystems(autonomic, motor,state-organizational,attentionandinteraction,and self-regulation).⁴⁰

Neonatal behavior is expressed through signs associated with each subsystem, which can be recognized by the parents, thus identifying the baby’s individualneeds,

respecting the rhythm of development and the adequate timeforstimulation,manipulation,andinteraction.⁴⁰Based onthistheory,mostoftheprogramsanalyzedwereaimedat improving reciprocity in parent/babyrelations,promoting thebaby’sself-regulationandbetterparentalunderstand- ingofthechild’sneeds.Betterunderstandingofthebaby’s communicationsignsfavorstheprovisionofpositivephysical andemotionalexperiencesforthechild,leadingtobetter neurodevelopment responses, includingthecognitive out- comeinthepreterminfantsample.

Similarly,intheoverallresult,earlyinterventionfocused on the family compared to the usual care improved the motor development of children born prematurely; however, when the analysis wasperformed at differentages, the effect was observed only at 12 months of age. Sim- ilar results were observed in the meta-analysisby Spittle etal.,¹⁸althoughtheydidnotspeciﬁcallyaddressinterven- tionsfocusedonthefamily,andbyVanderveenetal.,²²who found a positive effect onthe motor outcome only at 12 months.

Theinterventionsanalyzed inthe present study,which promoted greater beneﬁts in motor development, were those based mainly on the synchronous-active theory.

Although most of the programs analyzed are not speciﬁ- callyfocusedonmotordevelopment,theearlyintervention elements based onthe synchronous-active theory help to explaintheoverallpositiveeffectofan earlyintervention onthemotoroutcomeinthepreterminfantsample.

Whenthesocialriskwasaddedtothebiologicalrisk,no positiveeffectof theinterventionwasobservedonmotor developmentandcognition, evenwhen childrenwithhigh vs.lowsocialriskwerecompared.Itshouldbenotedthat the meta-analysis was performed by grouping data from onlytwostudieswithmoderatemethodologicalquality^5,31; therefore, the resultshould be interpreted with caution.

There isevidence thatmore intensive andlong-term programs,suchasEarlyHeadStart,⁴¹carriedoutintheUnited Stateswithmorethan3000childrenfromlow-incomefam- ilies in the ﬁrst 3 years of life, have a positive impact on cognitive development.It is possible that the number of sessions³¹ and the intensity⁵ of theinterventions were not sufﬁcient to affect the motor and cognitive development of children with associated social and biological risks.

Regardingthe languageoutcome, it wasobserved that earlyinterventioncomparedtousualcarewasnoteffective inimprovingthelanguageofpretermchildrenand/orthose atsocialrisk.However,languagewasevaluatedonlyinfour morerecentstudies,usingtheBayleyIIIscale^21,31,36andthe MacArthur-BatesShortFormoftheCDI.³⁹

TheBayleyIIscalewasappliedtotheothereightstudies, which consistsof mentalandpsychomotorscales, withno isolatedscoreforlanguage.Withtheavailabilityofspeciﬁc scalesforlanguageevaluation,itisimportanttoincludethis domaininclinicaltrials,soitwillbepossibletoanalyzethe impactofinterventionsonchildren’slanguage,contributing tothecreationofmoreefﬁcientprograms.

The interventions included in this meta-analysis were heterogeneousregardingtheirduration,numberofsessions andmethodsused.However,mostcasesincludedparental educationonhowtodealwithandstimulatetheirchildren in the different areas, based mainly on the synchronous-