Screening e diagnosi de diabete gestazionalenella pratica clinica:

Sempre valide le linee guida ?

Graziano Di Cianni Direttore UOC Diabetologia e Mal.

Metabolismo – ASL Toscana Nordovest “rete clinica diabetologica”

Dichiarazione Conflitti di Interesse

Il sottoscritto dott. Graziano Di Cianni

Dichiara Di aver avuto negli ultimi due anni i rapporti anche di finanziamento con i seguenti soggetti portatori di interessi commerciali in campo sanitario:

Eli Lilly, Novonordisk, SanofiMerck, Jansen, Novartis,

Mediolanum, Astrazeneca,TakedaJonshon & Jonson, Roche Diagnostics, Menarini

GDM Screening

1964O’Sullivan e Mahan

definisconoi criteri per il DG

1979NDDG modifica

i criteri proposti daO’Sullivan

201020001990198019701960

1980OMS

Propone criteri per il DG

1982Carpenter e Coustan

propongono una revisionedei criteri di O’Sullivan

1996EASD propone

nuovi criteriper il DG

2010IADPSG propone

nuovi criteri basatisullo studio HAPO

2013OMS

adottai criteri IADPSG

2011ADA approvaI Criteri IADPSG

1985OMS

rivede i criteri per il DGabbassando le soglie diagnostiche

a digiuno e a 2h1999OMS

rivede i criteri per il DGabbassando la soglie diagnostica

a digiuno

ADA: American Diabetes Association; EASD: European Association for the Study of Diabetes; IADPSG: International Association of theDiabetes and Pregnancy Study Groups; NDDG: National Diabetes Data Group; OMS: Organizzazione Mondiale della Sanità

Settembre 2011ISS-SID-AMD

stabiliscono unoscreening selettivo

• In March 2010, the International Association of Diabetes and Pregnancy Study Groups(IADPSG) recommendations were accepted in Italy.

• The use of these criteria resulted in higher rate of GDM.• As a consequence, the Italian Public Health Authority, in September 2011, issued more

restrictive guidelines

CURRENT PROTOCOLS FOR THE DIAGNOSIS OF GDM

IADPSGWHOAACEFIGO

Universal screening24-28 weeks

75grOGTT

ACOG Universalscreening24-28 weeks

50 gOGCT

100 gr OGTTIn positive cases

CDA Universal screening24-28 weeks

50 gOGCT

75 gr In positive cases

NICEADIPS

Selectivescreening At soon aspossible

75 grOGTT

Negative and at high risk75 grOGTT

ADA (2015) Declare one o two step proach is accetable

Screening for and diagnosis of GDM

ACOG and NIH still support the two-step approach with universal screening

ADA concludes that… IADPSG criteria may be the preferred approach

WHO 2013 vs VHO 1999 GDM +45%GDM by FPG 1 % vs 65%

GDM by 2h OGTT 97% vs 19%

WHO 1999 non consente la diagnosi di GDM (FPG) in donne obese che spesso sviluppano ipertensione; WHO 2013 esclude donne (2hOGTT) in cui il trattamento per GDM risulta efficace

High Risk (16th-18th weeks)OGTT according HAPO study

Medium Risk (24th-28th weeks)OGTT according HAPO study

Personal history of GDM Pre-pregnancy BMI ≥ 30 Kg/m2

FPG at the first visit 100-125mg/dl

Age ≥ 35 years Pre-pregnancy BMI ≥ 25 Kg/m2

Previous macrosomia Family history of diabetes Family from areas with a high

prevalence of diabetes

If OGTT is normal, women with these riskfactors must repeat the OGTT between24th and 28th gestational weeks

National Guidelines for GDM Screening in Italy (2011)Selective Screening

according risk factors

National Guidelines for GDM Screening in Italy (2011)

mg/dl mmol/lbasal 92 5.11-h 180 10.02-h 153 8.5

OGTT 75 g

According HAPO Study

Alla 1° visita FPG o RPG

Fattori di rischio

FPG ≥126mg/dl oRBG ≥200mg/dl o

HbA1c ≥6.5%

FPG 100-125mg/dl

o fattori di rischio

FPG<100 mg/dl + fattori di rischio

Diabete pregravidico

trattamento

OGTT 75g glucosio

Fra la 16 e 18°sett. gestazionale

OGTT 75g glucosio

Fra la 24 e 28°sett. gestazionale

National Guidelines for GDM Screening in Italy (2011)

BassoRischio Medio rischio Alto

ISS No screeening 24-28 settimane, - eta ≥35 anni - Sovrappesomacrosomia fetale in una gravidanza precedente- GDM in gravidanza precedente - anamnesi familiare DM 2Etnia ad elevata prevalenza

A 16-18 settimane : - Pregresso GDM- Obesità- Glicemia precedentemente/o all’inizio della gravidanza, di fra 100 e 125 mg/dl

ADA2010

No screeningGruppo etnico a bassa prevalenzaFamiliarità negativaAnamnesi ostetrica negativa per eventi sfavorevoliAnamesi negativa per intolleranza glucidicaEtà < 25 aaNormopeso

24-28 settimaneCaratteristiche intermedie

Appena possibile:Familiarità positivaPregressa GDMObesitàGlicosuria marcata nella gravidanza in corsoPregresso neonato macrosoma/LGAPCOS

NICE 2015

24-28 settimaneObesitàPregressa macrosomiaPregresso GDMFamiliarità per DM2Etnia ad elevato rischio

Appena possibilePregresso GDMGlicosuria nella gravidanza in corso

Stratificazione del rischio

Pregnancy outcomes after IADPSG recommendation

GDMn=2026

GDM ex NGTn=112

NGTn=1815

Delivery (g.w.) 38.6 ± 2.1 38.3 ± 2.9 38.7 ± 2.8Cesarean section(%) 41 * 43.6 * 31.1 *Fetal morbidity (%) 9.8 16.5 7.2Macrosomia (%) 9.2 10.8 7.9Birthweight (g) 3346 ± 519 3326 ± 590 3348 ± 478Babies’ length (cm) 49.2 ± 2.4 48.5 ± 3 49.4 ± 2.2Ponderal index (g/cm3) 2.81 ± 0.41 ** 2.95 ± 0.61 ** 2.77 ± 0.34 **LGA (%) 19.5 18.1 15SGA(%) 2.9 2.8 3.2

* p<0,005 ** p< 0,0001

Lapolla A Diabet Med,2011

«Overt Diabetes»:7.7%

GDM Prevalence 10.9% ( 25% greater as compared to the one determined with the old criteria10 years ago)

Early screening for high risk women is not applied

30% low-risk women with OGTT positive for GDM

Level of implementation of guidelines on screening and diagnosis of gestational diabetes: a national survey.

B. Pintaudi et al. (2015)Diabetes Research and Clinical Practice

REGIONE TOSCANA - PERCORSO ASSISTENZIALE DIABETE GESTAZIONALE

This is a retrospective study based on two administrative sources

A database of certificate of care and delivery (CEDAP) including informationabout pregnancy, delivery newborn and parentsA regional flux dataset of lab prescription including all prescriptions of OGTTperformed since the 16th gestational week from the 12 local health care units ofTuscany

All women who delivered in Tuscany in the year 2014 were identified by CEDAPand their data after excluding those with pregestational diabetes, were linkedto the regional flux of all specialists’ visit including prescription of OGTTperformed since the 16th week of gestation.

All pregnant women were classified as eligible and not eligible according toNGL.

In the two groups, for each stratum, a logistic regression was performed toevaluate the chance of being tested by the OGTT, after adjusting for maternalage, marital status, education degree, ancestry, employment status, parity,smoking habit, pregestational BMI, first visit setting.

METHODS

Women tested before 16th week: 94

22730 pregnant women

Total group of women who delivered in 2015 (n. 23270)

Medium-High risk women (Eligible for screening test) n. 12840 (56.4%)Low risk women (Non eligible for screening test) n. 9890 (43.5%)

Eligible10,015 (55.6%)

OGTT18006 (79.2%)

Women with pre-gestational diabetes: 446

No OGTT4724 (20.8%)

Not Eligible7,991 (44.4%)

Eligible2,825 (59.8%)

Not Eligible1,899 (40.2%)

Chance of being testes by the OGTT Logistic regression analysis

0

20

40

60

80

100

120

Eligible women Not eligible women

Late screeningEarly screening

3,95% 1,98%

TIME OF SCREENING TEST

STIMA DELLA PREVALENZA DEL DIABETE GESTAZIONALEDefinizione dell’algoritmo diagnostico

Donne che effettuano curva OGTT (flussi Spa)

+ almeno una delle seguenti condizioni

•Donne che effettuano terapia insulinica (flussi Spf e Fed)*•Donne che effettuano una visita diabetologica (flussi Spa)*•Donne che effettuano una terapia educazionale per diabete (flussi Spa)*•Donne che effettuano OGTT entro 6 mesi dal parto (flussi Spa)

* Data di erogazione prima del parto

VALIDATION OF GDM DIAGNOSIS

Total Cases with GDM, captured by algorithm

2000 (11.11%)

Group of eligible women who performed OGTT

n. 10015

Group of non eligible women who performed OGTT

n. 7991

GDM captured by algorithm1439 (14.37%)

GDM captured by algorithm561 (7%)

Fig. 2

GDM DIAGNOSIS

Prevalenza del Diabete GestazionalePer le donne che hanno effettuato screening eleggibili e non eleggibili

N. casi con GDM2000

(11,36%)

Elegibili 1439(14,37%)

Non Elegibili 561(7,02%)

Diabete Gestazionale in Trattamento Insulinico

N. casi611

(30,5%)

Elegibili 465(32,3%)

Non Elegibili 146(26 %)

Donne a basso Rischio per GDM che Non avrebbero dovuto eseguire lo screening secondo le Linee Guida Nazionali

•10816 Donne Non Eleggibili

•7991 Eseguono lo screening per GDM

•561 Diagnosi di GDM

•146 In trattamento Insulinico

Epoca del Parto in donne sottoposte a screening con e senza con GDM

< 32 settimane(%)

32-36 sett.(%)

≥ 37 sett.(%)

Donne con GDM

Eleggibili 0,6 11,5 88

Non Eleggibili

0,4 8,4 91,3

Donne no GDM

Eleggibili 1,0 7,2 91,7

Non Eleggibili

0,5 5,3 94,2

Spontaneo(%)

Operativo*(%)

Taglio Cesareo**(%)

Donne con GDM

Eleggibili 61,4 4,9 33,8

Non Eleggibili

64 5,7 30,4

Donne no GDM

Eleggibili 63,9 5,4 30,7

Non Eleggibili 72,9 5,8 21,2

*Parto Operativo = con uso di Forcipe o Ventosa**Taglio Cesareo d’elezione + in travaglio+ in urgenza

Modalità del Parto in donne sottoposte a screening con e senza con GDM

Maternal and fetal complications in women with gestational and pregestational diabetes

• 85075 parti 2012 – 2016 (identificati da CeDAP)In donne che hanno eseguito OGTT

– NGT (Normale OGTT) 76922– GDM (ldentificate mediante Algoritmo) 8153

– Pre-GDM (database regionale) 476* (solo 2 anni)

Pre-GDM and GDM vs NGT

Macrosomia

Pre – GDMGDM

IRR: 2.00 (CI 1.54-2.58) p < 0.001IRR: 0.89 (CI 0.81-0.98) p =0.02

Caesarean Section

Pre - GDM IRR: 1.28 (CI 1.05 – 1.57) p<0.001

GDM IRR: 1.11 (CI 1.05 – 1.17) p=0.02

Neonatal Distress (Apgar<7)

Pre – GDMGDM

IRR : 1,59 (CI 0.80-3.16) nsIRR: 1.12 (CI 0,92 -1.39) ns

Reduced risk of Macrosomia in GDM women: this suggest an effective prevention of this complication in our population

CONCLUSIONS

• In Tuscany glucose metabolism is being tested in aboutthe 80% of pregnancies

• Adhesion to guidelines is very low, with a large numberof women not elegible who have been tested

• Rate of GDM, calculated by a validate algorithm issimilar to the one found in other populations

• Insulin therapy is required in quite a third of GDM, including a significant number of not eligible women

This study represents an example of how significantinformation cam be obtained from administrativedatasets.

Only universal glucose screening in pregnancies seems to be effective to adequately capture all GDM cases.

CONCLUSIONS

Grazie per l’attenzione