7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 18

Research ArticleDiabetic Retinopathy in Pregnancy A Population-Based Study of

Women with Pregestational Diabetes

Aoife M Egan1 Lyle McVicker1 Adrienne Heerey1

Louise Carmody1 Fiona Harney2 and Fidelma P Dunne1

983089 Galway Diabetes Research Centre National University of Ireland Galway and University Hospital Galway Newcastle Galway Ireland 983090Department of Ophthalmology National University of Ireland Galway and University Hospital Galway Newcastle Galway Ireland

Correspondence should be addressed to Aoie M Egan aoieegangmailcom

Received 983089983095 February 983090983088983089983093 Revised 983090983093 March 983090983088983089983093 Accepted 983090983094 March 983090983088983089983093

Academic Editor Hiroshi Okamoto

Copyright copy 983090983088983089983093 Aoie M Egan et al Tis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Te aim o this observational study was to evaluate screening and progression o diabetic retinopathy during pregnancy in womenwith pregestational diabetes attending 1047297ve antenatal centres along the Irish Atlantic seaboard An adequate requency o screeningwas de1047297nedas at least tworetinal evaluations in separate trimesters Progression was de1047297ned as at least one stage o deterioration o diabetic retinopathy andor development o diabetic macular edema on at least one eye Women with pregestational diabetes whodelivered afer 983090983090 gestational weeks ( = 307) were included In total 983089983096983093 (983094983088983091) had an adequate number o retinal examinations

Attendance at prepregnancy care was associated with receiving adequate screening (odds ratio 983094983090983091 CI 983091983091983097ndash983089983089983092983094 (1038389 lt 0001

))Among those who received adequate evaluations ( = 185) 983092983096 (983090983093983097) had retinopathy progression Increasing booking systolicblood pressure (OR 983089983088983091 CI 983089983088983089ndash983089983088983094 1038389 = 002) and greater drop in HbA983089c between 1047297rst and third trimesters o pregnancy (OR 983090983088983093 CI 983089983088983097ndash983091983096983095 1038389 = 003) signi1047297cantly increased the odds o progression A signi1047297cant proportion o women continueto demonstrate retinopathy progression during pregnancy Tis study highlights the role o prepregnancy care and the importanceo close monitoring during pregnancy and identi1047297es those patients at the highest risk or retinopathy progression

1 Introduction

Deterioration o diabetic retinopathy during pregnancy iswell described in women with pregestational diabetes mel-litus [983089ndash983091] Tis progression is in1047298uenced by multiple ac-

tors including the pregnancy itsel glycemic control beoreand during pregnancy and the presence o preexistingretinopathy [983092 983093] Maternal medical complications includ-ing pregnancy-induced hypertension diabetic nephropathyand preeclampsia are also associated with progression o retinopathy [983094 983095] Unortunately study sample size hasrequently limited the evaluation o additional risk actorsand many studies predate the era o modern diabetes care inpregnancy which includes tight glycemic control and bloodpressure management [983089 983090 983096 983097] Additionally there is nodata on screening rates within populations or on actors asso-ciated with receiving adequate retinal examinations duringpregnancy

Te Atlantic Diabetes in Pregnancy (Atlantic DIP) initia-tive was established in 983090983088983088983093 and represents 1047297ve antenatal cen-ters along the Irish Atlantic seaboard covering a populationo 983093983088983088983088983088983088 mixed urban and rural dwellers Te group offerswomen specialist-led evidence-based care beore duringand afer pregnancy and has signi1047297cantly improved localoutcomes in women with diabetes in pregnancy [983089983088]

Te aim o this study was to review the requency o retinal examination during pregnancy in the Atlantic DIPcohort and examine maternal actors associated with receiv-ing the optimal number o examinations Additionally wedocumented the progression o diabetic retinopathy duringpregnancy and actors associated with this progression

2 Methods

983090983089 Study Design and Population Tis study was designedas an observational study o retinopathy status during

Hindawi Publishing CorporationJournal of Diabetes ResearchVolume 2015 Article ID 310239 7 pageshttpdxdoiorg1011552015310239

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 28

983090 Journal o Diabetes Research

983137983138983148983141 983089 Classi1047297cation o diabetic retinopathy [983089983090]

Grade Description Lesion

R983088 No retinopathy No apparent retinopathy

R983089 Background retinopathy Microaneurysm(s)

Retinal haemorrhage(s) plusmn any exudate

R983090 Preprolierative retinopathy Venous beading venous loop or reduplicationIntraretinal microvascular abnormality (IRMA)Multiple deep round or blot haemorrhages

R983091 Prolierative retinopathy

New vessels on disc (NVD)New vessels elsewhere (NVE)Preretinal or vitreous haemorrhagePreretinal 1047297brosis plusmn tractional retinal detachment

M983088 No maculopathy No apparent maculopathy

M983089 Maculopathy present

Exudate within 983089 disc diameter (DD) o the centre o the oveaCircinate or group o exudates within the maculaRetinal thickening within 983089 DD o the centre o the ovea (i stereo available)Any microaneurysms or haemorrhage within 983089 DD o the centre o the ovea only i associated with abest VA o le983094983089983090 (i no stereo)

pregnancy in women with pregestational diabetes Researchethics committee approval was obtained and women wererecruited between September 983090983088983088983094 and December 983090983088983089983090Women with singleton pregnancies who provided inormedconsent were included As per previous studies women wereclassi1047297ed as having pregestational diabetes on the ollowingbasis (983089) an established diagnosis o type one or type twodiabetes mellitus prior to conception or (983090) glycosylatedhemoglobin (HbA983089c) greater than 983094983093 in the 1047297rst trimester[983089983089] Data were collected rom study entry until 983089983090 weekspostpartum using an optimized digital database namely

DIAMOND (Hicom)

983090983090 Procedures Prior to pregnancy during annual review appointments all women were advised regarding the need toplan pregnancy and were offered the opportunity to attenda dedicated prepregnancy service During pregnancy eachwoman received standard advice on diet and exercise alongwith a dietician review Education was provided on sel-directed glucose monitoring and each woman was advised onglycemic targets Women were reviewed on a ortnightly basisand telephoned on a weekly basis Insulin was introduced(in the setting o type two diabetes mellitus) or adjusted i home glucose readings were outside the ollowing ranges on

more than three consecutive days asting glucose 983093983088 mmolLor a 983090-hour postprandial reading o 983095983088 mmolL Oral hypo-glycemic agents were not used during the study periodRetinal screening should occur at least twice during preg-nancy in separate trimesters and i established retinopathy is present then retinal examination should take place morerequently For the purposes o this study we accepted at leasttwo retinal evaluations in separate trimesters as adequateDuring the study period retinal examination took placein the locality o each antenatal center and results wereorwarded to the respective center At each visit visual acuity was measured bilaterally using the Snellen chart Te pupilswere then dilated with tropicamide 983089 and ophthalmological

examinations were perormed using a two-1047297eld photogra-phy system Tese images were reviewed by an accreditedretinal grader I photo screening was not perormed or i the images were abnormal an experienced ophthalmologistperormed an eye examination Progression was de1047297ned asat least one stage o deterioration o diabetic retinopathy andor development o diabetic macular edema on at leastone eye Grading standards as outlined by the NationalScreening Committee in the United Kingdom were ollowed(able 983089) [983089983090] Antihypertensive therapy was initiated whenblood pressure was ge983089983091983093983096983093 mmHg Labetalol was the 1047297rst-

choice antihypertensive agent ollowed by methyldopa whenneeded

983090983091 Statistical Analysis Data were analyzed using Statis-tical Package or the Social Sciences (SPSS) version 983090983088983088(IBM) Hypothesis testing was perormed on the data o equal variance and normal distribution using an unpairedStudentrsquos 1103925-test Te Mann-Whitney 907317 test was used asthe equivalent nonparametric test Chi squared analysiswas used to compare sample proportions Binary logisticregression was utilized to assess the association o multiplecovariates with receipt o adequate retinal evaluations andthe progression o retinopathy Data are expressed as means

plusmn standard deviation (SD) or the mean adjusted oddsratios (aORs) and 983097983093 con1047297dence intervals (CI) Statisticalsigni1047297cance was accepted when the 983097983093 CI did not containone (regression analysesratios) or zero (multiple groupcomparisonsmeans) Te signi1047297cance level () was acceptedwhen lt983088983088983093 or two-tailed analyses

3 Results

We identi1047297ed 983091983088983095 women with pregestational diabetes whodelivered afer 983090983090 gestational weeks rom the Atlantic DIPdatabase Tis cohort comprised 983090983088983096 (983094983095983096) with type onediabetes and 983097983097 (983091983090983090) with type two diabetes Te majority

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 38

Journal o Diabetes Research 983091

983137983138983148983141 983090 Characteristics o women who received an adequate number o retinal examinations versus those who did not ( = 307)

Adequate number o retinalexaminations

Inadequate number o retinal examinations

1038389 value

() 983089983096983093 (983094983088983091) 983089983090983090 (983091983097983095)

ype 983089 diabetes 983089983091983092 (983095983090983092) 983095983092 (983094983088983095)

ype 983090 diabetes 983093983089 (983090983095983094) 983092983096 (983091983097983091)Age (years) 983091983090983097 plusmn 983093983091 983091983089983093 plusmn 983093983092 983088983088983090

Gravida 983090983092 plusmn 983089983093 983090983096 plusmn 983090983090 983088983089983094

Parity 983088983097 plusmn 983089983089 983089983088 plusmn 983089983091 983088983089983091

Caucasian 983089983095983092 (983097983092983089) 983089983088983092 (983096983093983090) 983088983088983089

Diabetes duration (years) 983089983089983090983096 plusmn 983093983094983096 983097983090983093 plusmn 983093983095983095 983088983088983088983095

Nonsmokers 983089983093983096 (983096983093983092) 983089983089983088 (983097983088983090) 983088983090983097

Attendance at prepregnancy care 983089983088983096 (983093983096983092) 983090983089 (983089983095983090) lt983088983088983088983089

Folic acid 983089983090983097 (983094983097983095) 983094983094 (983093983092983089) 983088983088983088983089

983089st trimester HbA983089c (mmolmol) 983095983090983088 plusmn 983089983092983096 (983093983093983088 plusmn 983092983093) 983095983088983094 plusmn 983089983094983091 (983093983092983088 plusmn 983092983094) 983088983092983095

983091rd trimester HbA983089c (mmolmol) 983094983090983096 plusmn 983088983096983096 (983092983093983088 plusmn 983090983094) 983094983091983095 plusmn 983088983097983094 (983092983094983088 plusmn 983090983097) 983088983092983091

Years 983090983088983088983094ndash983090983088983088983096 983092983096 (983090983093983097) 983096983092 (983094983096983097)

Years 983090983088983088983097ndash983090983088983089983090 983089983091983095 (983095983092983089) 983091983096 (983091983089983089)

Data expressed as mean plusmn standard deviation (SD) number o patients and o group

o women were o Caucasian ethnicity ( = 278 983097983088983094)Tere were 983090983097983094 (983097983094983092) live births and 983089983089 (983091983094) stillbirths

Overall 983090983089983095 (983095983088983095) o 983091983088983095 women had retinal evaluationat least once during pregnancy and 983089983096983093 (983094983088983091) had anadequate number o examinations O the 983091983090 women who hadscreening on one occasion only 983090983097 (983097983088983094) had no retinopa-thy and 983091 (983097983092) had background retinopathy able 983090 out-lines the characteristics o those who received an adequatenumber o examinations versus those who did not Tosewho received an adequate number o retinal evaluations wereolder (329 plusmn 53 versus 315 plusmn 54 years 1038389 = 002) and ahigher proportion were o Caucasian ethnicity (983097983092983089 versus983096983093983090 1038389 = 001) Tere was no difference in gravida parity1047297rst or third trimester HbA983089c or smoking status between thetwo groups Among women with type one diabetes 983094983092983092received an adequate number o examinations comparedwith 983093983089983093 o women with type two diabetes A higherproportion o women who received appropriate screeninghad attended prepregnancy care (983093983096983092 versus 983089983095983090 1038389 lt

0001) and taken olic acid preconceptually (983094983097983095 versus983093983092983089 1038389 = 0001) A higher proportion o women receivedadequate examinations in the years 983090983088983088983097 to 983090983088983089983090 compared

with the years 983090983088983088983094 to 983090983088983088983096 (983095983092983089 versus 983090983093983097)A logistic regression model was completed to urther

examine maternal actors associated with receiving an ade-quate requency o ophthalmological evaluation in preg-nancy Te results are outlined in able 983091 and they identi1047297edattendance at prepregnancy care as the only maternal actorsigni1047297cantly associated with receiving appropriate screening(odds ratio 983094983090983091 CI 983091983091983097ndash983089983089983092983094 (1038389 lt 0001))

On evaluation o those patients who received two or moreretinal evaluations ( = 185) 983092983096 (983090983093983097) had retinopathy progression during pregnancy Tis represents 983089983093983094 o allincluded patients ( = 307) able 983092 urther outlines thecharacteristics o the women A higher proportion o women

983137983138983148983141 983091 Maternal actors associated with receiving appropriateretinal evaluation during pregnancy

Odds ratio Con1047297dence interval 1038389 value

Age 983089983088983090 983088983097983095ndash983089983088983096 983088983091983096

Ethnicity 983088983095983089 983088983090983095ndash983089983096983093 983088983092983096

Diabetes type 983088983097983093 983088983092983094ndash983089983097983096 983088983096983097

Diabetesduration

983089983088983091 983088983097983097ndash983089983088983095 983088983089983093

Attendance atprepregnancy care

983094983090983091 983091983091983097ndash983089983089983092983094 lt983088983088983088983089

Folic acid use 983088983097983095 983088983093983094ndash983089983094983095 983088983097983095

with type one diabetes progressed compared with type twodiabetes (983091983089983091 versus 983089983089983095 1038389 = 0001) Tose women whodemonstrated progression had on average a longer durationo diabetes (1443 plusmn 842 versus 979 plusmn 836 years 1038389 lt 0001)Although there was a higher requency o preeclampsia in thegroup that experienced progression this was not signi1047297cant

(983089983092983094 versus 983089983090983092 1038389 = 080) However those who didprogress had a signi1047297cantly higher systolic blood pressureat their initial antenatal visit (1286 plusmn 180 versus 1221 plusmn

130 mmHg 1038389 = 003) Additionally 1047297rst trimester HbA983089cwas higher (767 plusmn 162 versus 703 plusmn 139 1038389 = 001) andthe drop in HbA983089c between 1047297rst and third trimesters wasgreater (138 plusmn 133 versus 074 plusmn 090 1038389 = 0004) amongthose women who had disease progression Tere was nosigni1047297cant difference in rates o excessive gestational weightgain smoking status or body mass index between the twogroups

Logistic regression analysis revealed that increasing sys-tolic blood pressure at booking (OR 983089983088983091 CI 983089983088983089ndash983089983088983094

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 48

983092 Journal o Diabetes Research

983137983138983148983141 983092 Women who received appropriate screening ( = 185) Characteristics o those who demonstrated retinopathy progressioncompared with those who did not

No progression Progression 1038389 value

() 983089983091983095 (983095983092983089) 983092983096 (983090983093983097)

Diabetes type 983089 983097983090 (983094983095983090) 983092983090 (983096983095983093)

Diabetes type 983090 983092983093 (983091983090983096) 983094 (983089983090983093)

Age (years) 983091983090983094983092 plusmn 983093983091983093 983091983091983094983088 plusmn 983093983089983093 983088983090983096

Caucasian ethnicity 983089983090983096 (983097983091983092) 983092983094 (983097983093983096) 983088983093983092

Parity 983088983097983097 plusmn 983089983089983094 983088983095983091 plusmn 983089983088983093 983088983088983097

Gravida 983090983092983092 plusmn 983089983093983092 983090983090983089 plusmn 983089983093983091 983088983089983095

Body mass index (kgm983090) 983090983096983095983096 plusmn 983094983091983090 983090983095983093983088 plusmn 983093983091983088 983088983091983093

Prepregnancy care 983096983090 (983093983097983097) 983090983094 (983093983092983090) 983088983092983097

Folic acid 983097983095 (983095983088983096) 983091983090 (983094983094983095) 983088983093983097

Diabetes duration (years) 983097983095983097 plusmn 983096983091983094 983089983092983092983091 plusmn 983096983092983090 lt983088983088983088983089

Excessive weight gain in pregnancy 983095983094 (983093983093983093) 983090983097 (983094983088983092) 983088983096983096

983089st trimester 983095983088983091 plusmn 983089983091983097 983095983094983095 plusmn 983089983094983090983088983088983089

HbA983089c () (983093983091983088 plusmn 983092983090) (983094983088983088 plusmn 983092983097)

983091rd trimester 983094983090983095 plusmn 983088983097983091 983094983090983097 plusmn 983088983095983088983088983096983097HbA983089c () (983092983093983088 plusmn 983090983096) (983092983093983088 plusmn 983090983089)

Change in HbA983089c between 983089st and 983091rd trimester () 983088983095983092 plusmn 983088983097983088 (983097983094 plusmn 983089983089983095) 983089983091983096 plusmn 983089983091983091 (983089983095983097 plusmn 983089983095983091) 983088983088983088983092

Preeclampsia 983089983095 (983089983090983092) 983095 (983089983092983094) 983088983096983088

Systolic blood pressure at booking (mmHg) 983089983090983090983089 plusmn 983089983091983088 983089983090983096983094 plusmn 983089983096983088 983088983088983091

Diastolic blood pressure at booking (mmHg) 983095983090983096983097 plusmn 983089983088983091 983095983094983088 plusmn 983097983092 983088983095983091

Nonsmoker 983089983089983096 (983096983094983089) 983092983088 (983096983091983092) 983088983094983091

Baseline retinal 1047297ndings

R983088 (no retinopathy) 983096983090 (983093983097983097) 983091983090 (983094983094983095)

R983089 (background) 983091983091 (983090983092983089) 983097 (983089983096983096)

R983090 (preprolierative) 983094 (983092983092) 983092 (983096983091)

R983091 (prolierative) 983089983088 (983095983091) 983088 (983088)

Maculopathy 983094 (983092983092) 983091 (983094983091)

Data expressed as mean plusmn standard deviation (SD) number o patients and o group

983137983138983148983141 983093 Factors associated with retinopathy progression

Odds ratio CI 1038389 value

Duration o diabetes 983089983088983092 983088983097983097ndash983089983089983088 983088983089983090

Diabetes type 983088983092983095 983088983089983093ndash983089983093983092 983088983090983089

983089st trimester HbA983089c 983088983096983091 983088983093983091ndash983089983091983088 983088983092983090

HbA983089c reductionbetween 983089st and 983091rdtrimester

983090983088983093 983089983088983097ndash983091983096983095 983088983088983091

Systolic bloodpressure at booking

983089983088983091 983089983088983089ndash983089983088983094 983088983088983090

1038389 = 002) and greater drop in HbA983089c between 1047297rst and thirdtrimesters o pregnancy (OR 983090983088983093 CI 983089983088983097ndash983091983096983095 1038389 = 003)signi1047297cantly increased the odds o retinopathy progressionDuration o diabetes diabetes type and 1047297rst trimester HbA983089cwere not associated with increased odds o progression andthese results are outlined in able 983093

Baseline retinal 1047297ndings are outlined in able 983092 O thosewomen who developed progression ( = 48) 983091983090 (983094983094983095)

had no retinopathy at baseline A total o 983090983094 (983093983092983090) womenprogressed rom no retinopathy to level 983089 (background)retinopathy only A urther 983095 (983089983092983094) progressed rom level983089 to level 983090 (preprolierative) retinopathy and 983094 women(983089983090983093) progressed to level 983091 (prolierative) retinopathy andrequired laser therapy wo women in the latter group hadalso received prepregnancy laser therapy Finally 983094 (983089983090983093)women developed mild maculopathy and three (983094983091) expe-rienced a worsening o preexisting maculopathy and required

laser therapy Among the group with maculopathy develop-ment ( = 9) 983092 (983092983092983092) women received prepregnancy lasertherapy

4 Discussion

In an unselected population o women with pregestationaldiabetes we demonstrate that 983094983088983091 had an adequate num-ber o ophthalmological examinations during pregnancyAttendance at prepregnancy care was strongly associatedwith receiving adequate retinal evaluation in the subsequentpregnancy Despite intensive glycemic control and antihyper-tensive therapy as required progression o retinopathy was

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 58

Journal o Diabetes Research 983093

observed in 983089983092 o the total group and in 983090983094 o those whohad more than one retinal examination during pregnancy

Recommendations or retinopathy screening and man-agement in pregnancy vary signi1047297cantly Te AmericanDiabetes Association advises an eye examination in the1047297rst trimester with close ollow-up throughout pregnancy

[983089983091] Te National Institute or Health and Clinical Excel-lence (NICE) in the United Kingdom recommends retinalassessment ollowing the 1047297rst antenatal clinic appointmentand again at 983090983096 weeks i the 1047297rst assessment is normalI any diabetic retinopathy is present an additional retinalassessment should be perormed at 983089983094ndash983090983088 weeks [983089983092] Forthe purposes o this study we accepted a minimum o tworetinal evaluations in separate trimesters in accordance withlocal guidelines Unortunately despite the existence o theseguidelines there was no retinal evaluation in 983091983093o cases and

just one evaluation in a urther 983097 While many studies inthe area o diabetic retinopathy in pregnancy include selectedpatients with complete ophthalmological evaluations only [983089 983089983093] a study o women with type two diabetes reported thatonly 983095983091 had the available ophthalmological examinations[983090] In relation to this current study there is not an automaticrecall system or retinal evaluation in our antenatal centersand each woman must be reerred individually It is theopinion o the authors thatan automatic standardized systemo ollow-up as demonstrated by Hampshire et al wouldimprove screening and ollow-up rates [983092] Te majority o women who had just one eye examination were retinopathy-ree and the lack o ollow-up in later pregnancy may re1047298ect aperceived ldquominimal riskrdquo on behal o the patient and healthcare provider with more ocus being placed on those patientswith established retinopathy

Another interesting observation presented herein is theassociation between attendance at a prepregnancy care pro-gram and adequate retinal assessment in the subsequentpregnancy It is reasonable to assume that the educationalcomponent o the program inorms women o recommendedintervals or ophthalmology review during pregnancy andthese women are more likelyto ensurethey receive andattendappointments Te increased attendance at prepregnancy care undoubtedly explains the higher proportion o womentaking prepregnancy olic acid in the group who receivedadequate eye assessments during pregnancy Unortunatelywe do not have inormation regarding the exact timing o prepregnancy care and levels o metabolic control and bloodpressure at the time o attendance Although there was no

signi1047297cant difference in progression o retinopathy betweenpatients attending prepregnancy care and those who did notimproved metabolic control just beore pregnancy may havein1047298uenced retinopathy progression during the subsequentpregnancy Finally the higher rates o adequate screeningin the latter our years o the study re1047298ect improvements inclinical care delivery as the Atlantic DIP program becameestablished

Tis study highlights the ongoing risk o retinopathy progression during pregnancy particularly among womenwith type one diabetes Rasmussen et al evaluated 983096983088 patientswith type two diabetes and observed progression in 983089983092[983090] Vestgaard et al evaluated 983089983088983090 women with type one

diabetes and noted progression in 983090983095 [983094] Tese studiesdid not 1047297nd an association between glucose control andprogression o retinopathy but this may be due to very tight prepregnancy glycemic control or a type-two errordue to a lesser number o included subjects However ourobservations reinorce other published works that noted both

signi1047297cant and nonsigni1047297cant trends towards progression o retinopathy in the setting o a greater drop in HbA983089c duringthe pregnancy [983093 983089983093 983089983094] While the third trimester HbA983089c wassimilar between groups that did and did not progress in ourstudy the 1047297rst trimester value was on average 983088983093 higherin the group that developed retinopathy progression Teimportance o prepregnancy glycemic optimization shouldbe highlighted as it is associated with a tendency towardless progression o retinopathy compared with waiting untilpregnancy is con1047297rmed in type one diabetes [983090 983089983093] Inthe setting o an unplanned pregnancy with poor glycemiccontrol the authors believe that glycemic control shouldbe prioritized and appropriately optimized as the long-termconsequences o poor glycemic control during the pregnancy appear to outweigh those o retinopathy progression [983089983088983089983093 983089983095 983089983096] Tis issue has also received attention in studiesinvolving a more general diabetes population For examplealthough early worseningo diabetic retinopathy wasnotedina higher proportion o those assigned to intensive treatmentin the Diabetes Control andComplications rial (DCC) thelong-term bene1047297ts o intensive insulin treatment greatly out-weighed the risks o this early worsening [983089983097] Te associationbetween retinopathy progression and systolic blood pressureat booking is not unexpected as hypertensive disorders o pregnancy and indeed higher systolic blood pressure areactors known to negatively in1047298uence retinopathy [983095 983090983088 983090983089]

In relation to the complication severity two-thirds o women who experienced retinopathy progression developedbackground retinopathy only and no women with a normalretinal examination during trimester one developed sight-threatening disease or required laser therapy All women whodeveloped sight-threatening disease had signi1047297cant changesidenti1047297ed at baseline Tese 1047297ndings are reassuring partic-ularly as Hellstedt et al demonstrated a regression o mildretinopathy postpartum in a cohort o women with typeone diabetes [983090983090] A limitation o the study is that we donot have postpartum evaluations to determine the longer-term progression o retinopathy However Arun and aylorstudied women with type one diabetes or 983093 years aferdelivery and concluded that pregnancy is not associated with

postpartum worsening o retinopathy [983089983095] Additionally inthe Pittsburgh EDC pregnancy study it was observed thatthe overall prevalence o retinopathy in women with priorpregnancy was similar to that o matched nulliparous women[983089983096]

Overall this was a robust nested cohort analysis per-ormed retrospectively with data managed prospectively within the Atlantic DIP database Although the observa-tional study design has inherent limitations including thepotential in1047298uence o unmeasured covariates such as addi-tional medications we have used robust statistical methodsto evaluate rates o retinopathy progression and employedregression analysis to demonstrate actors associated with

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 68

983094 Journal o Diabetes Research

disease progression and adequate retinal evaluation duringpregnancy Te management o the patients included in thisstudy is a re1047298ection o real-lie clinical practice and involvespatients with both type one and type two diabetes with

varying durations o disease Te 1047297ndings are externally validparticularly in relation to other predominantly Caucasian

populations

5 Conclusions

In summary with the establishment o a structured ante-natal care program more women are receiving an adequatenumber o retinal examinations during pregnancy Te intro-duction o an automatic recall system has the potential toimprove service delivery A signi1047297cant proportion o womencontinue to experience deterioration in retinopathy duringpregnancy and this validates the need or close ollow-upFinally the importance o prepregnancy care to ully inormwomen o the need or more requent retinal assessments

during pregnancy and allow preconceptual optimization o glycemic control and blood pressure should be emphasizedTese results will assist the health care proessional designand provid high quality antenatal care or women withpregestational diabetes mellitus

Ethical Approval

Local ethics committee approval was obtained or this studyAll procedures ollowed were in accordance with the HelsinkiDeclaration o 983089983097983095983093 as revised in 983090983088983088983096

DisclosureTe Health Research Board o Ireland did not have a role inthe study design execution or data analysis and it did nothave a role in drafing the paper or the decision to submit thepaper or publication

Conflict of Interests

Te authors declare that there is no con1047298ict o interestsregarding the publication o this paper

Acknowledgment

Tis study was unded by the Health Research Board o Ireland

References

[983089] B E K Klein S E Moss and R Klein ldquoEffect o pregnancy onprogression o diabetic retinopathyrdquo Diabetes Care vol 983089983091 no983089 pp 983091983092ndash983092983088 983089983097983097983088

[983090] K L Rasmussen C S Laugesen L Ringholm M VestgaardP Damm and E R Mathiesen ldquoProgression o diabeticretinopathy during pregnancy in women with type 983090 diabetesrdquoDiabetologia vol 983093983091 no 983094 pp 983089983088983095983094ndash983089983088983096983091 983090983088983089983088

[983091] Y Omori S Minei estuo K Nemoto M Shimizu andM Sanaka ldquoCurrent status o pregnancy in diabetic womenA comparison o pregnancy in IDDM and NIDDM mothersrdquoDiabetes Research and Clinical Practice vol 983090983092 supplement ppS983090983095983091ndashS983090983095983096 983089983097983097983092

[983092] R Hampshire H Wharton R Leigh A Wright and PDodson ldquoScreening ordiabetic retinopathy in pregnancyusing

photographic review clinicsrdquo Diabetic Medicine vol 983091983088 no 983092pp 983092983095983093ndash983092983095983095 983090983088983089983091

[983093] E Y Chew J L Mills B E Metzger et al ldquoMetaboliccontrol and progression o retinopathy Te Diabetes in Early Pregnancy Study National Institute o Child Health and HumanDevelopment Diabetes in Early Pregnancy Studyrdquo DiabetesCare vol 983089983096 no 983093 pp 983094983091983089ndash983094983091983095 983089983097983097983093

[983094] M Vestgaard L Ringholm C S Laugesen K L RasmussenP Damm and E R Mathiesen ldquoPregnancy-induced sight-threatening diabetic retinopathy in women with ype 983089 dia-betesrdquo Diabetic Medicine vol 983090983095 no 983092 pp 983092983091983089ndash983092983091983093 983090983088983089983088

[983095] M Lovestam-Adrian C Agardh A Aberg and E AgardhldquoPre-eclampsia is a potent risk actor or deterioration o retinopathy during pregnancy in type 983089 diabetic patientsrdquoDiabetic Medicine vol 983089983092 no 983089983090 pp 983089983088983093983097ndash983089983088983094983093 983089983097983097983095

[983096] C M Dibble N K Kochenour R J Worley F H yler and MSwartz ldquoEffect o pregnancy on diabetic retinopathyrdquo Obstetricsamp Gynecology vol 983093983097 no 983094 pp 983094983097983097ndash983095983088983092 983089983097983096983090

[983097] J H Price D R Hadden D B Archer and J M G HarleyldquoDiabetic retinopathy in pregnancyrdquo British Journalof Obstetricsamp Gynaecology vol 983097983089 no 983089 pp 983089983089ndash983089983095 983089983097983096983092

[983089983088] L A Owens G Avalos B Kirwan L Carmody and F DunneldquoALANIC DIP closing the loop a change in clinical practicecan improve outcomes or women with pregestational diabetesrdquoDiabetes Care vol 983091983093 no 983096 pp 983089983094983094983097ndash983089983094983095983089 983090983088983089983090

[983089983089] A M Egan M C Dennedy W Al-Ramli A Heerey G Avalosand F Dunne ldquoALANIC-DIP excessive gestational weight

gain and pregnancy outcomes in women with gestational orpregestational diabetes mellitusrdquo Journal of Clinical Endocrinol-ogy and Metabolism vol 983097983097 no 983089 pp 983090983089983090ndash983090983089983097 983090983088983089983092

[983089983090] UK National Screening Committee EssentialElementsin Devel-oping a Diabetic Retinopathy Screening Programme NationalScreening Programme or Diabetic Retinopathy Workbook 983092983091983090983088983088983097

[983089983091] American Diabetes Association ldquoStandards o medical care indiabetesmdash983090983088983089983091rdquo Diabetes Care vol 983091983094 supplement 983089 pp S983089983089ndashS983094983094 983090983088983089983091

[983089983092] NICE guidelines [CG983094983091] Diabetes in pregnancy managemento diabetes and its complications rom pre-conception to thepostnatal period 983090983088983088983096 httpwwwniceorgukguidancecg983094983091chapterguidance

[983089983093] Te Diabetes Control and Complications rial Research GroupldquoEffect o pregnancy on microvascular complications in thediabetes control and complications trialrdquo Diabetes Care vol 983090983091no 983096 pp 983089983088983096983092ndash983089983088983097983089 983090983088983088983088

[983089983094] R C emple V A Aldridge M J Sampson R H GreenwoodP J Heyburn and A Glenn ldquoImpact o pregnancy on theprogression o diabetic retinopathy in ype 983089 diabetesrdquo Diabetic Medicine vol 983089983096 no 983095 pp 983093983095983091ndash983093983095983095 983090983088983088983089

[983089983095] C S Arun and R aylor ldquoIn1047298uence o pregnancy on long-term progressiono retinopathy in patientswith type 983089 diabetesrdquoDiabetologia vol 983093983089 no 983094 pp 983089983088983092983089ndash983089983088983092983093 983090983088983088983096

[983089983096] A Hemachandra D Ellis C E Lloyd and J Orchard ldquoTein1047298uence o pregnancy on IDDMcomplicationsrdquo Diabetes Care vol 983089983096 no 983095 pp 983097983093983088ndash983097983093983092 983089983097983097983093

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 78

Journal o Diabetes Research 983095

[983089983097] Te Diabetes Control and Complications rial Research GroupldquoEarly worsening o diabetic retinopathy in the diabetes controland complications trialrdquo Archives of Ophthalmology vol 983089983089983094 no983095 pp 983096983095983092ndash983096983096983094 983089983097983097983096

[983090983088] B Rosenn M Miodovnik G Kranias et al ldquoProgression o dia-betic retinopathy in pregnancy association with hypertensionin pregnancyrdquo American Journalof Obstetrics amp Gynecology vol983089983094983094 no 983092 pp 983089983090983089983092ndash983089983090983089983096 983089983097983097983090

[983090983089] R Axer-Siegel M Hod S Fink-Cohen et al ldquoDiabeticretinopathy during pregnancyrdquo Ophthalmology vol 983089983088983091 no 983089983089pp 983089983096983089983093ndash983089983096983089983097 983089983097983097983094

[983090983090] Hellstedt R Kaaja K eramo and I Immonen ldquoTe effecto pregnancy on mild diabetic retinopathyrdquo Graefersquos Archive for Clinical and Experimental Ophthalmology vol 983090983091983093 no 983095 pp983092983091983095ndash983092983092983089 983089983097983097983095

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 88

Submit your manuscripts at

httpwwwhindawicom

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 38

Journal o Diabetes Research 983091

983137983138983148983141 983090 Characteristics o women who received an adequate number o retinal examinations versus those who did not ( = 307)

Adequate number o retinalexaminations

Inadequate number o retinal examinations

1038389 value

() 983089983096983093 (983094983088983091) 983089983090983090 (983091983097983095)

ype 983089 diabetes 983089983091983092 (983095983090983092) 983095983092 (983094983088983095)

ype 983090 diabetes 983093983089 (983090983095983094) 983092983096 (983091983097983091)Age (years) 983091983090983097 plusmn 983093983091 983091983089983093 plusmn 983093983092 983088983088983090

Gravida 983090983092 plusmn 983089983093 983090983096 plusmn 983090983090 983088983089983094

Parity 983088983097 plusmn 983089983089 983089983088 plusmn 983089983091 983088983089983091

Caucasian 983089983095983092 (983097983092983089) 983089983088983092 (983096983093983090) 983088983088983089

Diabetes duration (years) 983089983089983090983096 plusmn 983093983094983096 983097983090983093 plusmn 983093983095983095 983088983088983088983095

Nonsmokers 983089983093983096 (983096983093983092) 983089983089983088 (983097983088983090) 983088983090983097

Attendance at prepregnancy care 983089983088983096 (983093983096983092) 983090983089 (983089983095983090) lt983088983088983088983089

Folic acid 983089983090983097 (983094983097983095) 983094983094 (983093983092983089) 983088983088983088983089

983089st trimester HbA983089c (mmolmol) 983095983090983088 plusmn 983089983092983096 (983093983093983088 plusmn 983092983093) 983095983088983094 plusmn 983089983094983091 (983093983092983088 plusmn 983092983094) 983088983092983095

983091rd trimester HbA983089c (mmolmol) 983094983090983096 plusmn 983088983096983096 (983092983093983088 plusmn 983090983094) 983094983091983095 plusmn 983088983097983094 (983092983094983088 plusmn 983090983097) 983088983092983091

Years 983090983088983088983094ndash983090983088983088983096 983092983096 (983090983093983097) 983096983092 (983094983096983097)

Years 983090983088983088983097ndash983090983088983089983090 983089983091983095 (983095983092983089) 983091983096 (983091983089983089)

Data expressed as mean plusmn standard deviation (SD) number o patients and o group

o women were o Caucasian ethnicity ( = 278 983097983088983094)Tere were 983090983097983094 (983097983094983092) live births and 983089983089 (983091983094) stillbirths

Overall 983090983089983095 (983095983088983095) o 983091983088983095 women had retinal evaluationat least once during pregnancy and 983089983096983093 (983094983088983091) had anadequate number o examinations O the 983091983090 women who hadscreening on one occasion only 983090983097 (983097983088983094) had no retinopa-thy and 983091 (983097983092) had background retinopathy able 983090 out-lines the characteristics o those who received an adequatenumber o examinations versus those who did not Tosewho received an adequate number o retinal evaluations wereolder (329 plusmn 53 versus 315 plusmn 54 years 1038389 = 002) and ahigher proportion were o Caucasian ethnicity (983097983092983089 versus983096983093983090 1038389 = 001) Tere was no difference in gravida parity1047297rst or third trimester HbA983089c or smoking status between thetwo groups Among women with type one diabetes 983094983092983092received an adequate number o examinations comparedwith 983093983089983093 o women with type two diabetes A higherproportion o women who received appropriate screeninghad attended prepregnancy care (983093983096983092 versus 983089983095983090 1038389 lt

0001) and taken olic acid preconceptually (983094983097983095 versus983093983092983089 1038389 = 0001) A higher proportion o women receivedadequate examinations in the years 983090983088983088983097 to 983090983088983089983090 compared

with the years 983090983088983088983094 to 983090983088983088983096 (983095983092983089 versus 983090983093983097)A logistic regression model was completed to urther

examine maternal actors associated with receiving an ade-quate requency o ophthalmological evaluation in preg-nancy Te results are outlined in able 983091 and they identi1047297edattendance at prepregnancy care as the only maternal actorsigni1047297cantly associated with receiving appropriate screening(odds ratio 983094983090983091 CI 983091983091983097ndash983089983089983092983094 (1038389 lt 0001))

On evaluation o those patients who received two or moreretinal evaluations ( = 185) 983092983096 (983090983093983097) had retinopathy progression during pregnancy Tis represents 983089983093983094 o allincluded patients ( = 307) able 983092 urther outlines thecharacteristics o the women A higher proportion o women

983137983138983148983141 983091 Maternal actors associated with receiving appropriateretinal evaluation during pregnancy

Odds ratio Con1047297dence interval 1038389 value

Age 983089983088983090 983088983097983095ndash983089983088983096 983088983091983096

Ethnicity 983088983095983089 983088983090983095ndash983089983096983093 983088983092983096

Diabetes type 983088983097983093 983088983092983094ndash983089983097983096 983088983096983097

Diabetesduration

983089983088983091 983088983097983097ndash983089983088983095 983088983089983093

Attendance atprepregnancy care

983094983090983091 983091983091983097ndash983089983089983092983094 lt983088983088983088983089

Folic acid use 983088983097983095 983088983093983094ndash983089983094983095 983088983097983095

with type one diabetes progressed compared with type twodiabetes (983091983089983091 versus 983089983089983095 1038389 = 0001) Tose women whodemonstrated progression had on average a longer durationo diabetes (1443 plusmn 842 versus 979 plusmn 836 years 1038389 lt 0001)Although there was a higher requency o preeclampsia in thegroup that experienced progression this was not signi1047297cant

(983089983092983094 versus 983089983090983092 1038389 = 080) However those who didprogress had a signi1047297cantly higher systolic blood pressureat their initial antenatal visit (1286 plusmn 180 versus 1221 plusmn

130 mmHg 1038389 = 003) Additionally 1047297rst trimester HbA983089cwas higher (767 plusmn 162 versus 703 plusmn 139 1038389 = 001) andthe drop in HbA983089c between 1047297rst and third trimesters wasgreater (138 plusmn 133 versus 074 plusmn 090 1038389 = 0004) amongthose women who had disease progression Tere was nosigni1047297cant difference in rates o excessive gestational weightgain smoking status or body mass index between the twogroups

Logistic regression analysis revealed that increasing sys-tolic blood pressure at booking (OR 983089983088983091 CI 983089983088983089ndash983089983088983094

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 48

983092 Journal o Diabetes Research

983137983138983148983141 983092 Women who received appropriate screening ( = 185) Characteristics o those who demonstrated retinopathy progressioncompared with those who did not

No progression Progression 1038389 value

() 983089983091983095 (983095983092983089) 983092983096 (983090983093983097)

Diabetes type 983089 983097983090 (983094983095983090) 983092983090 (983096983095983093)

Diabetes type 983090 983092983093 (983091983090983096) 983094 (983089983090983093)

Age (years) 983091983090983094983092 plusmn 983093983091983093 983091983091983094983088 plusmn 983093983089983093 983088983090983096

Caucasian ethnicity 983089983090983096 (983097983091983092) 983092983094 (983097983093983096) 983088983093983092

Parity 983088983097983097 plusmn 983089983089983094 983088983095983091 plusmn 983089983088983093 983088983088983097

Gravida 983090983092983092 plusmn 983089983093983092 983090983090983089 plusmn 983089983093983091 983088983089983095

Body mass index (kgm983090) 983090983096983095983096 plusmn 983094983091983090 983090983095983093983088 plusmn 983093983091983088 983088983091983093

Prepregnancy care 983096983090 (983093983097983097) 983090983094 (983093983092983090) 983088983092983097

Folic acid 983097983095 (983095983088983096) 983091983090 (983094983094983095) 983088983093983097

Diabetes duration (years) 983097983095983097 plusmn 983096983091983094 983089983092983092983091 plusmn 983096983092983090 lt983088983088983088983089

Excessive weight gain in pregnancy 983095983094 (983093983093983093) 983090983097 (983094983088983092) 983088983096983096

983089st trimester 983095983088983091 plusmn 983089983091983097 983095983094983095 plusmn 983089983094983090983088983088983089

HbA983089c () (983093983091983088 plusmn 983092983090) (983094983088983088 plusmn 983092983097)

983091rd trimester 983094983090983095 plusmn 983088983097983091 983094983090983097 plusmn 983088983095983088983088983096983097HbA983089c () (983092983093983088 plusmn 983090983096) (983092983093983088 plusmn 983090983089)

Change in HbA983089c between 983089st and 983091rd trimester () 983088983095983092 plusmn 983088983097983088 (983097983094 plusmn 983089983089983095) 983089983091983096 plusmn 983089983091983091 (983089983095983097 plusmn 983089983095983091) 983088983088983088983092

Preeclampsia 983089983095 (983089983090983092) 983095 (983089983092983094) 983088983096983088

Systolic blood pressure at booking (mmHg) 983089983090983090983089 plusmn 983089983091983088 983089983090983096983094 plusmn 983089983096983088 983088983088983091

Diastolic blood pressure at booking (mmHg) 983095983090983096983097 plusmn 983089983088983091 983095983094983088 plusmn 983097983092 983088983095983091

Nonsmoker 983089983089983096 (983096983094983089) 983092983088 (983096983091983092) 983088983094983091

Baseline retinal 1047297ndings

R983088 (no retinopathy) 983096983090 (983093983097983097) 983091983090 (983094983094983095)

R983089 (background) 983091983091 (983090983092983089) 983097 (983089983096983096)

R983090 (preprolierative) 983094 (983092983092) 983092 (983096983091)

R983091 (prolierative) 983089983088 (983095983091) 983088 (983088)

Maculopathy 983094 (983092983092) 983091 (983094983091)

Data expressed as mean plusmn standard deviation (SD) number o patients and o group

983137983138983148983141 983093 Factors associated with retinopathy progression

Odds ratio CI 1038389 value

Duration o diabetes 983089983088983092 983088983097983097ndash983089983089983088 983088983089983090

Diabetes type 983088983092983095 983088983089983093ndash983089983093983092 983088983090983089

983089st trimester HbA983089c 983088983096983091 983088983093983091ndash983089983091983088 983088983092983090

HbA983089c reductionbetween 983089st and 983091rdtrimester

983090983088983093 983089983088983097ndash983091983096983095 983088983088983091

Systolic bloodpressure at booking

983089983088983091 983089983088983089ndash983089983088983094 983088983088983090

1038389 = 002) and greater drop in HbA983089c between 1047297rst and thirdtrimesters o pregnancy (OR 983090983088983093 CI 983089983088983097ndash983091983096983095 1038389 = 003)signi1047297cantly increased the odds o retinopathy progressionDuration o diabetes diabetes type and 1047297rst trimester HbA983089cwere not associated with increased odds o progression andthese results are outlined in able 983093

Baseline retinal 1047297ndings are outlined in able 983092 O thosewomen who developed progression ( = 48) 983091983090 (983094983094983095)

had no retinopathy at baseline A total o 983090983094 (983093983092983090) womenprogressed rom no retinopathy to level 983089 (background)retinopathy only A urther 983095 (983089983092983094) progressed rom level983089 to level 983090 (preprolierative) retinopathy and 983094 women(983089983090983093) progressed to level 983091 (prolierative) retinopathy andrequired laser therapy wo women in the latter group hadalso received prepregnancy laser therapy Finally 983094 (983089983090983093)women developed mild maculopathy and three (983094983091) expe-rienced a worsening o preexisting maculopathy and required

laser therapy Among the group with maculopathy develop-ment ( = 9) 983092 (983092983092983092) women received prepregnancy lasertherapy

4 Discussion

In an unselected population o women with pregestationaldiabetes we demonstrate that 983094983088983091 had an adequate num-ber o ophthalmological examinations during pregnancyAttendance at prepregnancy care was strongly associatedwith receiving adequate retinal evaluation in the subsequentpregnancy Despite intensive glycemic control and antihyper-tensive therapy as required progression o retinopathy was

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 58

Journal o Diabetes Research 983093

observed in 983089983092 o the total group and in 983090983094 o those whohad more than one retinal examination during pregnancy

Recommendations or retinopathy screening and man-agement in pregnancy vary signi1047297cantly Te AmericanDiabetes Association advises an eye examination in the1047297rst trimester with close ollow-up throughout pregnancy

[983089983091] Te National Institute or Health and Clinical Excel-lence (NICE) in the United Kingdom recommends retinalassessment ollowing the 1047297rst antenatal clinic appointmentand again at 983090983096 weeks i the 1047297rst assessment is normalI any diabetic retinopathy is present an additional retinalassessment should be perormed at 983089983094ndash983090983088 weeks [983089983092] Forthe purposes o this study we accepted a minimum o tworetinal evaluations in separate trimesters in accordance withlocal guidelines Unortunately despite the existence o theseguidelines there was no retinal evaluation in 983091983093o cases and

just one evaluation in a urther 983097 While many studies inthe area o diabetic retinopathy in pregnancy include selectedpatients with complete ophthalmological evaluations only [983089 983089983093] a study o women with type two diabetes reported thatonly 983095983091 had the available ophthalmological examinations[983090] In relation to this current study there is not an automaticrecall system or retinal evaluation in our antenatal centersand each woman must be reerred individually It is theopinion o the authors thatan automatic standardized systemo ollow-up as demonstrated by Hampshire et al wouldimprove screening and ollow-up rates [983092] Te majority o women who had just one eye examination were retinopathy-ree and the lack o ollow-up in later pregnancy may re1047298ect aperceived ldquominimal riskrdquo on behal o the patient and healthcare provider with more ocus being placed on those patientswith established retinopathy

Another interesting observation presented herein is theassociation between attendance at a prepregnancy care pro-gram and adequate retinal assessment in the subsequentpregnancy It is reasonable to assume that the educationalcomponent o the program inorms women o recommendedintervals or ophthalmology review during pregnancy andthese women are more likelyto ensurethey receive andattendappointments Te increased attendance at prepregnancy care undoubtedly explains the higher proportion o womentaking prepregnancy olic acid in the group who receivedadequate eye assessments during pregnancy Unortunatelywe do not have inormation regarding the exact timing o prepregnancy care and levels o metabolic control and bloodpressure at the time o attendance Although there was no

signi1047297cant difference in progression o retinopathy betweenpatients attending prepregnancy care and those who did notimproved metabolic control just beore pregnancy may havein1047298uenced retinopathy progression during the subsequentpregnancy Finally the higher rates o adequate screeningin the latter our years o the study re1047298ect improvements inclinical care delivery as the Atlantic DIP program becameestablished

Tis study highlights the ongoing risk o retinopathy progression during pregnancy particularly among womenwith type one diabetes Rasmussen et al evaluated 983096983088 patientswith type two diabetes and observed progression in 983089983092[983090] Vestgaard et al evaluated 983089983088983090 women with type one

diabetes and noted progression in 983090983095 [983094] Tese studiesdid not 1047297nd an association between glucose control andprogression o retinopathy but this may be due to very tight prepregnancy glycemic control or a type-two errordue to a lesser number o included subjects However ourobservations reinorce other published works that noted both

signi1047297cant and nonsigni1047297cant trends towards progression o retinopathy in the setting o a greater drop in HbA983089c duringthe pregnancy [983093 983089983093 983089983094] While the third trimester HbA983089c wassimilar between groups that did and did not progress in ourstudy the 1047297rst trimester value was on average 983088983093 higherin the group that developed retinopathy progression Teimportance o prepregnancy glycemic optimization shouldbe highlighted as it is associated with a tendency towardless progression o retinopathy compared with waiting untilpregnancy is con1047297rmed in type one diabetes [983090 983089983093] Inthe setting o an unplanned pregnancy with poor glycemiccontrol the authors believe that glycemic control shouldbe prioritized and appropriately optimized as the long-termconsequences o poor glycemic control during the pregnancy appear to outweigh those o retinopathy progression [983089983088983089983093 983089983095 983089983096] Tis issue has also received attention in studiesinvolving a more general diabetes population For examplealthough early worseningo diabetic retinopathy wasnotedina higher proportion o those assigned to intensive treatmentin the Diabetes Control andComplications rial (DCC) thelong-term bene1047297ts o intensive insulin treatment greatly out-weighed the risks o this early worsening [983089983097] Te associationbetween retinopathy progression and systolic blood pressureat booking is not unexpected as hypertensive disorders o pregnancy and indeed higher systolic blood pressure areactors known to negatively in1047298uence retinopathy [983095 983090983088 983090983089]

In relation to the complication severity two-thirds o women who experienced retinopathy progression developedbackground retinopathy only and no women with a normalretinal examination during trimester one developed sight-threatening disease or required laser therapy All women whodeveloped sight-threatening disease had signi1047297cant changesidenti1047297ed at baseline Tese 1047297ndings are reassuring partic-ularly as Hellstedt et al demonstrated a regression o mildretinopathy postpartum in a cohort o women with typeone diabetes [983090983090] A limitation o the study is that we donot have postpartum evaluations to determine the longer-term progression o retinopathy However Arun and aylorstudied women with type one diabetes or 983093 years aferdelivery and concluded that pregnancy is not associated with

postpartum worsening o retinopathy [983089983095] Additionally inthe Pittsburgh EDC pregnancy study it was observed thatthe overall prevalence o retinopathy in women with priorpregnancy was similar to that o matched nulliparous women[983089983096]

Overall this was a robust nested cohort analysis per-ormed retrospectively with data managed prospectively within the Atlantic DIP database Although the observa-tional study design has inherent limitations including thepotential in1047298uence o unmeasured covariates such as addi-tional medications we have used robust statistical methodsto evaluate rates o retinopathy progression and employedregression analysis to demonstrate actors associated with

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 68

983094 Journal o Diabetes Research

disease progression and adequate retinal evaluation duringpregnancy Te management o the patients included in thisstudy is a re1047298ection o real-lie clinical practice and involvespatients with both type one and type two diabetes with

varying durations o disease Te 1047297ndings are externally validparticularly in relation to other predominantly Caucasian

populations

5 Conclusions

In summary with the establishment o a structured ante-natal care program more women are receiving an adequatenumber o retinal examinations during pregnancy Te intro-duction o an automatic recall system has the potential toimprove service delivery A signi1047297cant proportion o womencontinue to experience deterioration in retinopathy duringpregnancy and this validates the need or close ollow-upFinally the importance o prepregnancy care to ully inormwomen o the need or more requent retinal assessments

during pregnancy and allow preconceptual optimization o glycemic control and blood pressure should be emphasizedTese results will assist the health care proessional designand provid high quality antenatal care or women withpregestational diabetes mellitus

Ethical Approval

Local ethics committee approval was obtained or this studyAll procedures ollowed were in accordance with the HelsinkiDeclaration o 983089983097983095983093 as revised in 983090983088983088983096

DisclosureTe Health Research Board o Ireland did not have a role inthe study design execution or data analysis and it did nothave a role in drafing the paper or the decision to submit thepaper or publication

Conflict of Interests

Te authors declare that there is no con1047298ict o interestsregarding the publication o this paper

Acknowledgment

Tis study was unded by the Health Research Board o Ireland

References

[983089] B E K Klein S E Moss and R Klein ldquoEffect o pregnancy onprogression o diabetic retinopathyrdquo Diabetes Care vol 983089983091 no983089 pp 983091983092ndash983092983088 983089983097983097983088

[983090] K L Rasmussen C S Laugesen L Ringholm M VestgaardP Damm and E R Mathiesen ldquoProgression o diabeticretinopathy during pregnancy in women with type 983090 diabetesrdquoDiabetologia vol 983093983091 no 983094 pp 983089983088983095983094ndash983089983088983096983091 983090983088983089983088

[983091] Y Omori S Minei estuo K Nemoto M Shimizu andM Sanaka ldquoCurrent status o pregnancy in diabetic womenA comparison o pregnancy in IDDM and NIDDM mothersrdquoDiabetes Research and Clinical Practice vol 983090983092 supplement ppS983090983095983091ndashS983090983095983096 983089983097983097983092

[983092] R Hampshire H Wharton R Leigh A Wright and PDodson ldquoScreening ordiabetic retinopathy in pregnancyusing

photographic review clinicsrdquo Diabetic Medicine vol 983091983088 no 983092pp 983092983095983093ndash983092983095983095 983090983088983089983091

[983093] E Y Chew J L Mills B E Metzger et al ldquoMetaboliccontrol and progression o retinopathy Te Diabetes in Early Pregnancy Study National Institute o Child Health and HumanDevelopment Diabetes in Early Pregnancy Studyrdquo DiabetesCare vol 983089983096 no 983093 pp 983094983091983089ndash983094983091983095 983089983097983097983093

[983094] M Vestgaard L Ringholm C S Laugesen K L RasmussenP Damm and E R Mathiesen ldquoPregnancy-induced sight-threatening diabetic retinopathy in women with ype 983089 dia-betesrdquo Diabetic Medicine vol 983090983095 no 983092 pp 983092983091983089ndash983092983091983093 983090983088983089983088

[983095] M Lovestam-Adrian C Agardh A Aberg and E AgardhldquoPre-eclampsia is a potent risk actor or deterioration o retinopathy during pregnancy in type 983089 diabetic patientsrdquoDiabetic Medicine vol 983089983092 no 983089983090 pp 983089983088983093983097ndash983089983088983094983093 983089983097983097983095

[983096] C M Dibble N K Kochenour R J Worley F H yler and MSwartz ldquoEffect o pregnancy on diabetic retinopathyrdquo Obstetricsamp Gynecology vol 983093983097 no 983094 pp 983094983097983097ndash983095983088983092 983089983097983096983090

[983097] J H Price D R Hadden D B Archer and J M G HarleyldquoDiabetic retinopathy in pregnancyrdquo British Journalof Obstetricsamp Gynaecology vol 983097983089 no 983089 pp 983089983089ndash983089983095 983089983097983096983092

[983089983088] L A Owens G Avalos B Kirwan L Carmody and F DunneldquoALANIC DIP closing the loop a change in clinical practicecan improve outcomes or women with pregestational diabetesrdquoDiabetes Care vol 983091983093 no 983096 pp 983089983094983094983097ndash983089983094983095983089 983090983088983089983090

[983089983089] A M Egan M C Dennedy W Al-Ramli A Heerey G Avalosand F Dunne ldquoALANIC-DIP excessive gestational weight

gain and pregnancy outcomes in women with gestational orpregestational diabetes mellitusrdquo Journal of Clinical Endocrinol-ogy and Metabolism vol 983097983097 no 983089 pp 983090983089983090ndash983090983089983097 983090983088983089983092

[983089983090] UK National Screening Committee EssentialElementsin Devel-oping a Diabetic Retinopathy Screening Programme NationalScreening Programme or Diabetic Retinopathy Workbook 983092983091983090983088983088983097

[983089983091] American Diabetes Association ldquoStandards o medical care indiabetesmdash983090983088983089983091rdquo Diabetes Care vol 983091983094 supplement 983089 pp S983089983089ndashS983094983094 983090983088983089983091

[983089983092] NICE guidelines [CG983094983091] Diabetes in pregnancy managemento diabetes and its complications rom pre-conception to thepostnatal period 983090983088983088983096 httpwwwniceorgukguidancecg983094983091chapterguidance

[983089983093] Te Diabetes Control and Complications rial Research GroupldquoEffect o pregnancy on microvascular complications in thediabetes control and complications trialrdquo Diabetes Care vol 983090983091no 983096 pp 983089983088983096983092ndash983089983088983097983089 983090983088983088983088

[983089983094] R C emple V A Aldridge M J Sampson R H GreenwoodP J Heyburn and A Glenn ldquoImpact o pregnancy on theprogression o diabetic retinopathy in ype 983089 diabetesrdquo Diabetic Medicine vol 983089983096 no 983095 pp 983093983095983091ndash983093983095983095 983090983088983088983089

[983089983095] C S Arun and R aylor ldquoIn1047298uence o pregnancy on long-term progressiono retinopathy in patientswith type 983089 diabetesrdquoDiabetologia vol 983093983089 no 983094 pp 983089983088983092983089ndash983089983088983092983093 983090983088983088983096

[983089983096] A Hemachandra D Ellis C E Lloyd and J Orchard ldquoTein1047298uence o pregnancy on IDDMcomplicationsrdquo Diabetes Care vol 983089983096 no 983095 pp 983097983093983088ndash983097983093983092 983089983097983097983093

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 78

Journal o Diabetes Research 983095

[983089983097] Te Diabetes Control and Complications rial Research GroupldquoEarly worsening o diabetic retinopathy in the diabetes controland complications trialrdquo Archives of Ophthalmology vol 983089983089983094 no983095 pp 983096983095983092ndash983096983096983094 983089983097983097983096

[983090983088] B Rosenn M Miodovnik G Kranias et al ldquoProgression o dia-betic retinopathy in pregnancy association with hypertensionin pregnancyrdquo American Journalof Obstetrics amp Gynecology vol983089983094983094 no 983092 pp 983089983090983089983092ndash983089983090983089983096 983089983097983097983090

[983090983089] R Axer-Siegel M Hod S Fink-Cohen et al ldquoDiabeticretinopathy during pregnancyrdquo Ophthalmology vol 983089983088983091 no 983089983089pp 983089983096983089983093ndash983089983096983089983097 983089983097983097983094

[983090983090] Hellstedt R Kaaja K eramo and I Immonen ldquoTe effecto pregnancy on mild diabetic retinopathyrdquo Graefersquos Archive for Clinical and Experimental Ophthalmology vol 983090983091983093 no 983095 pp983092983091983095ndash983092983092983089 983089983097983097983095

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 88

Submit your manuscripts at

httpwwwhindawicom

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 48

983092 Journal o Diabetes Research

983137983138983148983141 983092 Women who received appropriate screening ( = 185) Characteristics o those who demonstrated retinopathy progressioncompared with those who did not

No progression Progression 1038389 value

() 983089983091983095 (983095983092983089) 983092983096 (983090983093983097)

Diabetes type 983089 983097983090 (983094983095983090) 983092983090 (983096983095983093)

Diabetes type 983090 983092983093 (983091983090983096) 983094 (983089983090983093)

Age (years) 983091983090983094983092 plusmn 983093983091983093 983091983091983094983088 plusmn 983093983089983093 983088983090983096

Caucasian ethnicity 983089983090983096 (983097983091983092) 983092983094 (983097983093983096) 983088983093983092

Parity 983088983097983097 plusmn 983089983089983094 983088983095983091 plusmn 983089983088983093 983088983088983097

Gravida 983090983092983092 plusmn 983089983093983092 983090983090983089 plusmn 983089983093983091 983088983089983095

Body mass index (kgm983090) 983090983096983095983096 plusmn 983094983091983090 983090983095983093983088 plusmn 983093983091983088 983088983091983093

Prepregnancy care 983096983090 (983093983097983097) 983090983094 (983093983092983090) 983088983092983097

Folic acid 983097983095 (983095983088983096) 983091983090 (983094983094983095) 983088983093983097

Diabetes duration (years) 983097983095983097 plusmn 983096983091983094 983089983092983092983091 plusmn 983096983092983090 lt983088983088983088983089

Excessive weight gain in pregnancy 983095983094 (983093983093983093) 983090983097 (983094983088983092) 983088983096983096

983089st trimester 983095983088983091 plusmn 983089983091983097 983095983094983095 plusmn 983089983094983090983088983088983089

HbA983089c () (983093983091983088 plusmn 983092983090) (983094983088983088 plusmn 983092983097)

983091rd trimester 983094983090983095 plusmn 983088983097983091 983094983090983097 plusmn 983088983095983088983088983096983097HbA983089c () (983092983093983088 plusmn 983090983096) (983092983093983088 plusmn 983090983089)

Change in HbA983089c between 983089st and 983091rd trimester () 983088983095983092 plusmn 983088983097983088 (983097983094 plusmn 983089983089983095) 983089983091983096 plusmn 983089983091983091 (983089983095983097 plusmn 983089983095983091) 983088983088983088983092

Preeclampsia 983089983095 (983089983090983092) 983095 (983089983092983094) 983088983096983088

Systolic blood pressure at booking (mmHg) 983089983090983090983089 plusmn 983089983091983088 983089983090983096983094 plusmn 983089983096983088 983088983088983091

Diastolic blood pressure at booking (mmHg) 983095983090983096983097 plusmn 983089983088983091 983095983094983088 plusmn 983097983092 983088983095983091

Nonsmoker 983089983089983096 (983096983094983089) 983092983088 (983096983091983092) 983088983094983091

Baseline retinal 1047297ndings

R983088 (no retinopathy) 983096983090 (983093983097983097) 983091983090 (983094983094983095)

R983089 (background) 983091983091 (983090983092983089) 983097 (983089983096983096)

R983090 (preprolierative) 983094 (983092983092) 983092 (983096983091)

R983091 (prolierative) 983089983088 (983095983091) 983088 (983088)

Maculopathy 983094 (983092983092) 983091 (983094983091)

Data expressed as mean plusmn standard deviation (SD) number o patients and o group

983137983138983148983141 983093 Factors associated with retinopathy progression

Odds ratio CI 1038389 value

Duration o diabetes 983089983088983092 983088983097983097ndash983089983089983088 983088983089983090

Diabetes type 983088983092983095 983088983089983093ndash983089983093983092 983088983090983089

983089st trimester HbA983089c 983088983096983091 983088983093983091ndash983089983091983088 983088983092983090

HbA983089c reductionbetween 983089st and 983091rdtrimester

983090983088983093 983089983088983097ndash983091983096983095 983088983088983091

Systolic bloodpressure at booking

983089983088983091 983089983088983089ndash983089983088983094 983088983088983090

1038389 = 002) and greater drop in HbA983089c between 1047297rst and thirdtrimesters o pregnancy (OR 983090983088983093 CI 983089983088983097ndash983091983096983095 1038389 = 003)signi1047297cantly increased the odds o retinopathy progressionDuration o diabetes diabetes type and 1047297rst trimester HbA983089cwere not associated with increased odds o progression andthese results are outlined in able 983093

Baseline retinal 1047297ndings are outlined in able 983092 O thosewomen who developed progression ( = 48) 983091983090 (983094983094983095)

had no retinopathy at baseline A total o 983090983094 (983093983092983090) womenprogressed rom no retinopathy to level 983089 (background)retinopathy only A urther 983095 (983089983092983094) progressed rom level983089 to level 983090 (preprolierative) retinopathy and 983094 women(983089983090983093) progressed to level 983091 (prolierative) retinopathy andrequired laser therapy wo women in the latter group hadalso received prepregnancy laser therapy Finally 983094 (983089983090983093)women developed mild maculopathy and three (983094983091) expe-rienced a worsening o preexisting maculopathy and required

laser therapy Among the group with maculopathy develop-ment ( = 9) 983092 (983092983092983092) women received prepregnancy lasertherapy

4 Discussion

In an unselected population o women with pregestationaldiabetes we demonstrate that 983094983088983091 had an adequate num-ber o ophthalmological examinations during pregnancyAttendance at prepregnancy care was strongly associatedwith receiving adequate retinal evaluation in the subsequentpregnancy Despite intensive glycemic control and antihyper-tensive therapy as required progression o retinopathy was

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 58

Journal o Diabetes Research 983093

observed in 983089983092 o the total group and in 983090983094 o those whohad more than one retinal examination during pregnancy

Recommendations or retinopathy screening and man-agement in pregnancy vary signi1047297cantly Te AmericanDiabetes Association advises an eye examination in the1047297rst trimester with close ollow-up throughout pregnancy

[983089983091] Te National Institute or Health and Clinical Excel-lence (NICE) in the United Kingdom recommends retinalassessment ollowing the 1047297rst antenatal clinic appointmentand again at 983090983096 weeks i the 1047297rst assessment is normalI any diabetic retinopathy is present an additional retinalassessment should be perormed at 983089983094ndash983090983088 weeks [983089983092] Forthe purposes o this study we accepted a minimum o tworetinal evaluations in separate trimesters in accordance withlocal guidelines Unortunately despite the existence o theseguidelines there was no retinal evaluation in 983091983093o cases and

just one evaluation in a urther 983097 While many studies inthe area o diabetic retinopathy in pregnancy include selectedpatients with complete ophthalmological evaluations only [983089 983089983093] a study o women with type two diabetes reported thatonly 983095983091 had the available ophthalmological examinations[983090] In relation to this current study there is not an automaticrecall system or retinal evaluation in our antenatal centersand each woman must be reerred individually It is theopinion o the authors thatan automatic standardized systemo ollow-up as demonstrated by Hampshire et al wouldimprove screening and ollow-up rates [983092] Te majority o women who had just one eye examination were retinopathy-ree and the lack o ollow-up in later pregnancy may re1047298ect aperceived ldquominimal riskrdquo on behal o the patient and healthcare provider with more ocus being placed on those patientswith established retinopathy

Another interesting observation presented herein is theassociation between attendance at a prepregnancy care pro-gram and adequate retinal assessment in the subsequentpregnancy It is reasonable to assume that the educationalcomponent o the program inorms women o recommendedintervals or ophthalmology review during pregnancy andthese women are more likelyto ensurethey receive andattendappointments Te increased attendance at prepregnancy care undoubtedly explains the higher proportion o womentaking prepregnancy olic acid in the group who receivedadequate eye assessments during pregnancy Unortunatelywe do not have inormation regarding the exact timing o prepregnancy care and levels o metabolic control and bloodpressure at the time o attendance Although there was no

signi1047297cant difference in progression o retinopathy betweenpatients attending prepregnancy care and those who did notimproved metabolic control just beore pregnancy may havein1047298uenced retinopathy progression during the subsequentpregnancy Finally the higher rates o adequate screeningin the latter our years o the study re1047298ect improvements inclinical care delivery as the Atlantic DIP program becameestablished

Tis study highlights the ongoing risk o retinopathy progression during pregnancy particularly among womenwith type one diabetes Rasmussen et al evaluated 983096983088 patientswith type two diabetes and observed progression in 983089983092[983090] Vestgaard et al evaluated 983089983088983090 women with type one

diabetes and noted progression in 983090983095 [983094] Tese studiesdid not 1047297nd an association between glucose control andprogression o retinopathy but this may be due to very tight prepregnancy glycemic control or a type-two errordue to a lesser number o included subjects However ourobservations reinorce other published works that noted both

signi1047297cant and nonsigni1047297cant trends towards progression o retinopathy in the setting o a greater drop in HbA983089c duringthe pregnancy [983093 983089983093 983089983094] While the third trimester HbA983089c wassimilar between groups that did and did not progress in ourstudy the 1047297rst trimester value was on average 983088983093 higherin the group that developed retinopathy progression Teimportance o prepregnancy glycemic optimization shouldbe highlighted as it is associated with a tendency towardless progression o retinopathy compared with waiting untilpregnancy is con1047297rmed in type one diabetes [983090 983089983093] Inthe setting o an unplanned pregnancy with poor glycemiccontrol the authors believe that glycemic control shouldbe prioritized and appropriately optimized as the long-termconsequences o poor glycemic control during the pregnancy appear to outweigh those o retinopathy progression [983089983088983089983093 983089983095 983089983096] Tis issue has also received attention in studiesinvolving a more general diabetes population For examplealthough early worseningo diabetic retinopathy wasnotedina higher proportion o those assigned to intensive treatmentin the Diabetes Control andComplications rial (DCC) thelong-term bene1047297ts o intensive insulin treatment greatly out-weighed the risks o this early worsening [983089983097] Te associationbetween retinopathy progression and systolic blood pressureat booking is not unexpected as hypertensive disorders o pregnancy and indeed higher systolic blood pressure areactors known to negatively in1047298uence retinopathy [983095 983090983088 983090983089]

In relation to the complication severity two-thirds o women who experienced retinopathy progression developedbackground retinopathy only and no women with a normalretinal examination during trimester one developed sight-threatening disease or required laser therapy All women whodeveloped sight-threatening disease had signi1047297cant changesidenti1047297ed at baseline Tese 1047297ndings are reassuring partic-ularly as Hellstedt et al demonstrated a regression o mildretinopathy postpartum in a cohort o women with typeone diabetes [983090983090] A limitation o the study is that we donot have postpartum evaluations to determine the longer-term progression o retinopathy However Arun and aylorstudied women with type one diabetes or 983093 years aferdelivery and concluded that pregnancy is not associated with

postpartum worsening o retinopathy [983089983095] Additionally inthe Pittsburgh EDC pregnancy study it was observed thatthe overall prevalence o retinopathy in women with priorpregnancy was similar to that o matched nulliparous women[983089983096]

Overall this was a robust nested cohort analysis per-ormed retrospectively with data managed prospectively within the Atlantic DIP database Although the observa-tional study design has inherent limitations including thepotential in1047298uence o unmeasured covariates such as addi-tional medications we have used robust statistical methodsto evaluate rates o retinopathy progression and employedregression analysis to demonstrate actors associated with

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 68

983094 Journal o Diabetes Research

disease progression and adequate retinal evaluation duringpregnancy Te management o the patients included in thisstudy is a re1047298ection o real-lie clinical practice and involvespatients with both type one and type two diabetes with

varying durations o disease Te 1047297ndings are externally validparticularly in relation to other predominantly Caucasian

populations

5 Conclusions

In summary with the establishment o a structured ante-natal care program more women are receiving an adequatenumber o retinal examinations during pregnancy Te intro-duction o an automatic recall system has the potential toimprove service delivery A signi1047297cant proportion o womencontinue to experience deterioration in retinopathy duringpregnancy and this validates the need or close ollow-upFinally the importance o prepregnancy care to ully inormwomen o the need or more requent retinal assessments

during pregnancy and allow preconceptual optimization o glycemic control and blood pressure should be emphasizedTese results will assist the health care proessional designand provid high quality antenatal care or women withpregestational diabetes mellitus

Ethical Approval

Local ethics committee approval was obtained or this studyAll procedures ollowed were in accordance with the HelsinkiDeclaration o 983089983097983095983093 as revised in 983090983088983088983096

DisclosureTe Health Research Board o Ireland did not have a role inthe study design execution or data analysis and it did nothave a role in drafing the paper or the decision to submit thepaper or publication

Conflict of Interests

Te authors declare that there is no con1047298ict o interestsregarding the publication o this paper

Acknowledgment

Tis study was unded by the Health Research Board o Ireland

References

[983089] B E K Klein S E Moss and R Klein ldquoEffect o pregnancy onprogression o diabetic retinopathyrdquo Diabetes Care vol 983089983091 no983089 pp 983091983092ndash983092983088 983089983097983097983088

[983090] K L Rasmussen C S Laugesen L Ringholm M VestgaardP Damm and E R Mathiesen ldquoProgression o diabeticretinopathy during pregnancy in women with type 983090 diabetesrdquoDiabetologia vol 983093983091 no 983094 pp 983089983088983095983094ndash983089983088983096983091 983090983088983089983088

[983091] Y Omori S Minei estuo K Nemoto M Shimizu andM Sanaka ldquoCurrent status o pregnancy in diabetic womenA comparison o pregnancy in IDDM and NIDDM mothersrdquoDiabetes Research and Clinical Practice vol 983090983092 supplement ppS983090983095983091ndashS983090983095983096 983089983097983097983092

[983092] R Hampshire H Wharton R Leigh A Wright and PDodson ldquoScreening ordiabetic retinopathy in pregnancyusing

photographic review clinicsrdquo Diabetic Medicine vol 983091983088 no 983092pp 983092983095983093ndash983092983095983095 983090983088983089983091

[983093] E Y Chew J L Mills B E Metzger et al ldquoMetaboliccontrol and progression o retinopathy Te Diabetes in Early Pregnancy Study National Institute o Child Health and HumanDevelopment Diabetes in Early Pregnancy Studyrdquo DiabetesCare vol 983089983096 no 983093 pp 983094983091983089ndash983094983091983095 983089983097983097983093

[983094] M Vestgaard L Ringholm C S Laugesen K L RasmussenP Damm and E R Mathiesen ldquoPregnancy-induced sight-threatening diabetic retinopathy in women with ype 983089 dia-betesrdquo Diabetic Medicine vol 983090983095 no 983092 pp 983092983091983089ndash983092983091983093 983090983088983089983088

[983095] M Lovestam-Adrian C Agardh A Aberg and E AgardhldquoPre-eclampsia is a potent risk actor or deterioration o retinopathy during pregnancy in type 983089 diabetic patientsrdquoDiabetic Medicine vol 983089983092 no 983089983090 pp 983089983088983093983097ndash983089983088983094983093 983089983097983097983095

[983096] C M Dibble N K Kochenour R J Worley F H yler and MSwartz ldquoEffect o pregnancy on diabetic retinopathyrdquo Obstetricsamp Gynecology vol 983093983097 no 983094 pp 983094983097983097ndash983095983088983092 983089983097983096983090

[983097] J H Price D R Hadden D B Archer and J M G HarleyldquoDiabetic retinopathy in pregnancyrdquo British Journalof Obstetricsamp Gynaecology vol 983097983089 no 983089 pp 983089983089ndash983089983095 983089983097983096983092

[983089983088] L A Owens G Avalos B Kirwan L Carmody and F DunneldquoALANIC DIP closing the loop a change in clinical practicecan improve outcomes or women with pregestational diabetesrdquoDiabetes Care vol 983091983093 no 983096 pp 983089983094983094983097ndash983089983094983095983089 983090983088983089983090

[983089983089] A M Egan M C Dennedy W Al-Ramli A Heerey G Avalosand F Dunne ldquoALANIC-DIP excessive gestational weight

gain and pregnancy outcomes in women with gestational orpregestational diabetes mellitusrdquo Journal of Clinical Endocrinol-ogy and Metabolism vol 983097983097 no 983089 pp 983090983089983090ndash983090983089983097 983090983088983089983092

[983089983090] UK National Screening Committee EssentialElementsin Devel-oping a Diabetic Retinopathy Screening Programme NationalScreening Programme or Diabetic Retinopathy Workbook 983092983091983090983088983088983097

[983089983091] American Diabetes Association ldquoStandards o medical care indiabetesmdash983090983088983089983091rdquo Diabetes Care vol 983091983094 supplement 983089 pp S983089983089ndashS983094983094 983090983088983089983091

[983089983092] NICE guidelines [CG983094983091] Diabetes in pregnancy managemento diabetes and its complications rom pre-conception to thepostnatal period 983090983088983088983096 httpwwwniceorgukguidancecg983094983091chapterguidance

[983089983093] Te Diabetes Control and Complications rial Research GroupldquoEffect o pregnancy on microvascular complications in thediabetes control and complications trialrdquo Diabetes Care vol 983090983091no 983096 pp 983089983088983096983092ndash983089983088983097983089 983090983088983088983088

[983089983094] R C emple V A Aldridge M J Sampson R H GreenwoodP J Heyburn and A Glenn ldquoImpact o pregnancy on theprogression o diabetic retinopathy in ype 983089 diabetesrdquo Diabetic Medicine vol 983089983096 no 983095 pp 983093983095983091ndash983093983095983095 983090983088983088983089

[983089983095] C S Arun and R aylor ldquoIn1047298uence o pregnancy on long-term progressiono retinopathy in patientswith type 983089 diabetesrdquoDiabetologia vol 983093983089 no 983094 pp 983089983088983092983089ndash983089983088983092983093 983090983088983088983096

[983089983096] A Hemachandra D Ellis C E Lloyd and J Orchard ldquoTein1047298uence o pregnancy on IDDMcomplicationsrdquo Diabetes Care vol 983089983096 no 983095 pp 983097983093983088ndash983097983093983092 983089983097983097983093

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 78

Journal o Diabetes Research 983095

[983089983097] Te Diabetes Control and Complications rial Research GroupldquoEarly worsening o diabetic retinopathy in the diabetes controland complications trialrdquo Archives of Ophthalmology vol 983089983089983094 no983095 pp 983096983095983092ndash983096983096983094 983089983097983097983096

[983090983088] B Rosenn M Miodovnik G Kranias et al ldquoProgression o dia-betic retinopathy in pregnancy association with hypertensionin pregnancyrdquo American Journalof Obstetrics amp Gynecology vol983089983094983094 no 983092 pp 983089983090983089983092ndash983089983090983089983096 983089983097983097983090

[983090983089] R Axer-Siegel M Hod S Fink-Cohen et al ldquoDiabeticretinopathy during pregnancyrdquo Ophthalmology vol 983089983088983091 no 983089983089pp 983089983096983089983093ndash983089983096983089983097 983089983097983097983094

[983090983090] Hellstedt R Kaaja K eramo and I Immonen ldquoTe effecto pregnancy on mild diabetic retinopathyrdquo Graefersquos Archive for Clinical and Experimental Ophthalmology vol 983090983091983093 no 983095 pp983092983091983095ndash983092983092983089 983089983097983097983095

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 88

Submit your manuscripts at

httpwwwhindawicom

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 58

Journal o Diabetes Research 983093

observed in 983089983092 o the total group and in 983090983094 o those whohad more than one retinal examination during pregnancy

Recommendations or retinopathy screening and man-agement in pregnancy vary signi1047297cantly Te AmericanDiabetes Association advises an eye examination in the1047297rst trimester with close ollow-up throughout pregnancy

[983089983091] Te National Institute or Health and Clinical Excel-lence (NICE) in the United Kingdom recommends retinalassessment ollowing the 1047297rst antenatal clinic appointmentand again at 983090983096 weeks i the 1047297rst assessment is normalI any diabetic retinopathy is present an additional retinalassessment should be perormed at 983089983094ndash983090983088 weeks [983089983092] Forthe purposes o this study we accepted a minimum o tworetinal evaluations in separate trimesters in accordance withlocal guidelines Unortunately despite the existence o theseguidelines there was no retinal evaluation in 983091983093o cases and

just one evaluation in a urther 983097 While many studies inthe area o diabetic retinopathy in pregnancy include selectedpatients with complete ophthalmological evaluations only [983089 983089983093] a study o women with type two diabetes reported thatonly 983095983091 had the available ophthalmological examinations[983090] In relation to this current study there is not an automaticrecall system or retinal evaluation in our antenatal centersand each woman must be reerred individually It is theopinion o the authors thatan automatic standardized systemo ollow-up as demonstrated by Hampshire et al wouldimprove screening and ollow-up rates [983092] Te majority o women who had just one eye examination were retinopathy-ree and the lack o ollow-up in later pregnancy may re1047298ect aperceived ldquominimal riskrdquo on behal o the patient and healthcare provider with more ocus being placed on those patientswith established retinopathy

Another interesting observation presented herein is theassociation between attendance at a prepregnancy care pro-gram and adequate retinal assessment in the subsequentpregnancy It is reasonable to assume that the educationalcomponent o the program inorms women o recommendedintervals or ophthalmology review during pregnancy andthese women are more likelyto ensurethey receive andattendappointments Te increased attendance at prepregnancy care undoubtedly explains the higher proportion o womentaking prepregnancy olic acid in the group who receivedadequate eye assessments during pregnancy Unortunatelywe do not have inormation regarding the exact timing o prepregnancy care and levels o metabolic control and bloodpressure at the time o attendance Although there was no

signi1047297cant difference in progression o retinopathy betweenpatients attending prepregnancy care and those who did notimproved metabolic control just beore pregnancy may havein1047298uenced retinopathy progression during the subsequentpregnancy Finally the higher rates o adequate screeningin the latter our years o the study re1047298ect improvements inclinical care delivery as the Atlantic DIP program becameestablished

Tis study highlights the ongoing risk o retinopathy progression during pregnancy particularly among womenwith type one diabetes Rasmussen et al evaluated 983096983088 patientswith type two diabetes and observed progression in 983089983092[983090] Vestgaard et al evaluated 983089983088983090 women with type one

diabetes and noted progression in 983090983095 [983094] Tese studiesdid not 1047297nd an association between glucose control andprogression o retinopathy but this may be due to very tight prepregnancy glycemic control or a type-two errordue to a lesser number o included subjects However ourobservations reinorce other published works that noted both

signi1047297cant and nonsigni1047297cant trends towards progression o retinopathy in the setting o a greater drop in HbA983089c duringthe pregnancy [983093 983089983093 983089983094] While the third trimester HbA983089c wassimilar between groups that did and did not progress in ourstudy the 1047297rst trimester value was on average 983088983093 higherin the group that developed retinopathy progression Teimportance o prepregnancy glycemic optimization shouldbe highlighted as it is associated with a tendency towardless progression o retinopathy compared with waiting untilpregnancy is con1047297rmed in type one diabetes [983090 983089983093] Inthe setting o an unplanned pregnancy with poor glycemiccontrol the authors believe that glycemic control shouldbe prioritized and appropriately optimized as the long-termconsequences o poor glycemic control during the pregnancy appear to outweigh those o retinopathy progression [983089983088983089983093 983089983095 983089983096] Tis issue has also received attention in studiesinvolving a more general diabetes population For examplealthough early worseningo diabetic retinopathy wasnotedina higher proportion o those assigned to intensive treatmentin the Diabetes Control andComplications rial (DCC) thelong-term bene1047297ts o intensive insulin treatment greatly out-weighed the risks o this early worsening [983089983097] Te associationbetween retinopathy progression and systolic blood pressureat booking is not unexpected as hypertensive disorders o pregnancy and indeed higher systolic blood pressure areactors known to negatively in1047298uence retinopathy [983095 983090983088 983090983089]

In relation to the complication severity two-thirds o women who experienced retinopathy progression developedbackground retinopathy only and no women with a normalretinal examination during trimester one developed sight-threatening disease or required laser therapy All women whodeveloped sight-threatening disease had signi1047297cant changesidenti1047297ed at baseline Tese 1047297ndings are reassuring partic-ularly as Hellstedt et al demonstrated a regression o mildretinopathy postpartum in a cohort o women with typeone diabetes [983090983090] A limitation o the study is that we donot have postpartum evaluations to determine the longer-term progression o retinopathy However Arun and aylorstudied women with type one diabetes or 983093 years aferdelivery and concluded that pregnancy is not associated with

postpartum worsening o retinopathy [983089983095] Additionally inthe Pittsburgh EDC pregnancy study it was observed thatthe overall prevalence o retinopathy in women with priorpregnancy was similar to that o matched nulliparous women[983089983096]

Overall this was a robust nested cohort analysis per-ormed retrospectively with data managed prospectively within the Atlantic DIP database Although the observa-tional study design has inherent limitations including thepotential in1047298uence o unmeasured covariates such as addi-tional medications we have used robust statistical methodsto evaluate rates o retinopathy progression and employedregression analysis to demonstrate actors associated with

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 68

983094 Journal o Diabetes Research

disease progression and adequate retinal evaluation duringpregnancy Te management o the patients included in thisstudy is a re1047298ection o real-lie clinical practice and involvespatients with both type one and type two diabetes with

varying durations o disease Te 1047297ndings are externally validparticularly in relation to other predominantly Caucasian

populations

5 Conclusions

In summary with the establishment o a structured ante-natal care program more women are receiving an adequatenumber o retinal examinations during pregnancy Te intro-duction o an automatic recall system has the potential toimprove service delivery A signi1047297cant proportion o womencontinue to experience deterioration in retinopathy duringpregnancy and this validates the need or close ollow-upFinally the importance o prepregnancy care to ully inormwomen o the need or more requent retinal assessments

during pregnancy and allow preconceptual optimization o glycemic control and blood pressure should be emphasizedTese results will assist the health care proessional designand provid high quality antenatal care or women withpregestational diabetes mellitus

Ethical Approval

Local ethics committee approval was obtained or this studyAll procedures ollowed were in accordance with the HelsinkiDeclaration o 983089983097983095983093 as revised in 983090983088983088983096

DisclosureTe Health Research Board o Ireland did not have a role inthe study design execution or data analysis and it did nothave a role in drafing the paper or the decision to submit thepaper or publication

Conflict of Interests

Te authors declare that there is no con1047298ict o interestsregarding the publication o this paper

Acknowledgment

Tis study was unded by the Health Research Board o Ireland

References

[983089] B E K Klein S E Moss and R Klein ldquoEffect o pregnancy onprogression o diabetic retinopathyrdquo Diabetes Care vol 983089983091 no983089 pp 983091983092ndash983092983088 983089983097983097983088

[983090] K L Rasmussen C S Laugesen L Ringholm M VestgaardP Damm and E R Mathiesen ldquoProgression o diabeticretinopathy during pregnancy in women with type 983090 diabetesrdquoDiabetologia vol 983093983091 no 983094 pp 983089983088983095983094ndash983089983088983096983091 983090983088983089983088

[983091] Y Omori S Minei estuo K Nemoto M Shimizu andM Sanaka ldquoCurrent status o pregnancy in diabetic womenA comparison o pregnancy in IDDM and NIDDM mothersrdquoDiabetes Research and Clinical Practice vol 983090983092 supplement ppS983090983095983091ndashS983090983095983096 983089983097983097983092

[983092] R Hampshire H Wharton R Leigh A Wright and PDodson ldquoScreening ordiabetic retinopathy in pregnancyusing

photographic review clinicsrdquo Diabetic Medicine vol 983091983088 no 983092pp 983092983095983093ndash983092983095983095 983090983088983089983091

[983093] E Y Chew J L Mills B E Metzger et al ldquoMetaboliccontrol and progression o retinopathy Te Diabetes in Early Pregnancy Study National Institute o Child Health and HumanDevelopment Diabetes in Early Pregnancy Studyrdquo DiabetesCare vol 983089983096 no 983093 pp 983094983091983089ndash983094983091983095 983089983097983097983093

[983094] M Vestgaard L Ringholm C S Laugesen K L RasmussenP Damm and E R Mathiesen ldquoPregnancy-induced sight-threatening diabetic retinopathy in women with ype 983089 dia-betesrdquo Diabetic Medicine vol 983090983095 no 983092 pp 983092983091983089ndash983092983091983093 983090983088983089983088

[983095] M Lovestam-Adrian C Agardh A Aberg and E AgardhldquoPre-eclampsia is a potent risk actor or deterioration o retinopathy during pregnancy in type 983089 diabetic patientsrdquoDiabetic Medicine vol 983089983092 no 983089983090 pp 983089983088983093983097ndash983089983088983094983093 983089983097983097983095

[983096] C M Dibble N K Kochenour R J Worley F H yler and MSwartz ldquoEffect o pregnancy on diabetic retinopathyrdquo Obstetricsamp Gynecology vol 983093983097 no 983094 pp 983094983097983097ndash983095983088983092 983089983097983096983090

[983097] J H Price D R Hadden D B Archer and J M G HarleyldquoDiabetic retinopathy in pregnancyrdquo British Journalof Obstetricsamp Gynaecology vol 983097983089 no 983089 pp 983089983089ndash983089983095 983089983097983096983092

[983089983088] L A Owens G Avalos B Kirwan L Carmody and F DunneldquoALANIC DIP closing the loop a change in clinical practicecan improve outcomes or women with pregestational diabetesrdquoDiabetes Care vol 983091983093 no 983096 pp 983089983094983094983097ndash983089983094983095983089 983090983088983089983090

[983089983089] A M Egan M C Dennedy W Al-Ramli A Heerey G Avalosand F Dunne ldquoALANIC-DIP excessive gestational weight

gain and pregnancy outcomes in women with gestational orpregestational diabetes mellitusrdquo Journal of Clinical Endocrinol-ogy and Metabolism vol 983097983097 no 983089 pp 983090983089983090ndash983090983089983097 983090983088983089983092

[983089983090] UK National Screening Committee EssentialElementsin Devel-oping a Diabetic Retinopathy Screening Programme NationalScreening Programme or Diabetic Retinopathy Workbook 983092983091983090983088983088983097

[983089983091] American Diabetes Association ldquoStandards o medical care indiabetesmdash983090983088983089983091rdquo Diabetes Care vol 983091983094 supplement 983089 pp S983089983089ndashS983094983094 983090983088983089983091

[983089983092] NICE guidelines [CG983094983091] Diabetes in pregnancy managemento diabetes and its complications rom pre-conception to thepostnatal period 983090983088983088983096 httpwwwniceorgukguidancecg983094983091chapterguidance

[983089983093] Te Diabetes Control and Complications rial Research GroupldquoEffect o pregnancy on microvascular complications in thediabetes control and complications trialrdquo Diabetes Care vol 983090983091no 983096 pp 983089983088983096983092ndash983089983088983097983089 983090983088983088983088

[983089983094] R C emple V A Aldridge M J Sampson R H GreenwoodP J Heyburn and A Glenn ldquoImpact o pregnancy on theprogression o diabetic retinopathy in ype 983089 diabetesrdquo Diabetic Medicine vol 983089983096 no 983095 pp 983093983095983091ndash983093983095983095 983090983088983088983089

[983089983095] C S Arun and R aylor ldquoIn1047298uence o pregnancy on long-term progressiono retinopathy in patientswith type 983089 diabetesrdquoDiabetologia vol 983093983089 no 983094 pp 983089983088983092983089ndash983089983088983092983093 983090983088983088983096

[983089983096] A Hemachandra D Ellis C E Lloyd and J Orchard ldquoTein1047298uence o pregnancy on IDDMcomplicationsrdquo Diabetes Care vol 983089983096 no 983095 pp 983097983093983088ndash983097983093983092 983089983097983097983093

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 78

Journal o Diabetes Research 983095

[983089983097] Te Diabetes Control and Complications rial Research GroupldquoEarly worsening o diabetic retinopathy in the diabetes controland complications trialrdquo Archives of Ophthalmology vol 983089983089983094 no983095 pp 983096983095983092ndash983096983096983094 983089983097983097983096

[983090983088] B Rosenn M Miodovnik G Kranias et al ldquoProgression o dia-betic retinopathy in pregnancy association with hypertensionin pregnancyrdquo American Journalof Obstetrics amp Gynecology vol983089983094983094 no 983092 pp 983089983090983089983092ndash983089983090983089983096 983089983097983097983090

[983090983089] R Axer-Siegel M Hod S Fink-Cohen et al ldquoDiabeticretinopathy during pregnancyrdquo Ophthalmology vol 983089983088983091 no 983089983089pp 983089983096983089983093ndash983089983096983089983097 983089983097983097983094

[983090983090] Hellstedt R Kaaja K eramo and I Immonen ldquoTe effecto pregnancy on mild diabetic retinopathyrdquo Graefersquos Archive for Clinical and Experimental Ophthalmology vol 983090983091983093 no 983095 pp983092983091983095ndash983092983092983089 983089983097983097983095

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 88

Submit your manuscripts at

httpwwwhindawicom

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 68

983094 Journal o Diabetes Research

disease progression and adequate retinal evaluation duringpregnancy Te management o the patients included in thisstudy is a re1047298ection o real-lie clinical practice and involvespatients with both type one and type two diabetes with

varying durations o disease Te 1047297ndings are externally validparticularly in relation to other predominantly Caucasian

populations

5 Conclusions

In summary with the establishment o a structured ante-natal care program more women are receiving an adequatenumber o retinal examinations during pregnancy Te intro-duction o an automatic recall system has the potential toimprove service delivery A signi1047297cant proportion o womencontinue to experience deterioration in retinopathy duringpregnancy and this validates the need or close ollow-upFinally the importance o prepregnancy care to ully inormwomen o the need or more requent retinal assessments

during pregnancy and allow preconceptual optimization o glycemic control and blood pressure should be emphasizedTese results will assist the health care proessional designand provid high quality antenatal care or women withpregestational diabetes mellitus

Ethical Approval

Local ethics committee approval was obtained or this studyAll procedures ollowed were in accordance with the HelsinkiDeclaration o 983089983097983095983093 as revised in 983090983088983088983096

DisclosureTe Health Research Board o Ireland did not have a role inthe study design execution or data analysis and it did nothave a role in drafing the paper or the decision to submit thepaper or publication

Conflict of Interests

Te authors declare that there is no con1047298ict o interestsregarding the publication o this paper

Acknowledgment

Tis study was unded by the Health Research Board o Ireland

References

[983089] B E K Klein S E Moss and R Klein ldquoEffect o pregnancy onprogression o diabetic retinopathyrdquo Diabetes Care vol 983089983091 no983089 pp 983091983092ndash983092983088 983089983097983097983088

[983090] K L Rasmussen C S Laugesen L Ringholm M VestgaardP Damm and E R Mathiesen ldquoProgression o diabeticretinopathy during pregnancy in women with type 983090 diabetesrdquoDiabetologia vol 983093983091 no 983094 pp 983089983088983095983094ndash983089983088983096983091 983090983088983089983088

[983091] Y Omori S Minei estuo K Nemoto M Shimizu andM Sanaka ldquoCurrent status o pregnancy in diabetic womenA comparison o pregnancy in IDDM and NIDDM mothersrdquoDiabetes Research and Clinical Practice vol 983090983092 supplement ppS983090983095983091ndashS983090983095983096 983089983097983097983092

[983092] R Hampshire H Wharton R Leigh A Wright and PDodson ldquoScreening ordiabetic retinopathy in pregnancyusing

photographic review clinicsrdquo Diabetic Medicine vol 983091983088 no 983092pp 983092983095983093ndash983092983095983095 983090983088983089983091

[983093] E Y Chew J L Mills B E Metzger et al ldquoMetaboliccontrol and progression o retinopathy Te Diabetes in Early Pregnancy Study National Institute o Child Health and HumanDevelopment Diabetes in Early Pregnancy Studyrdquo DiabetesCare vol 983089983096 no 983093 pp 983094983091983089ndash983094983091983095 983089983097983097983093

[983094] M Vestgaard L Ringholm C S Laugesen K L RasmussenP Damm and E R Mathiesen ldquoPregnancy-induced sight-threatening diabetic retinopathy in women with ype 983089 dia-betesrdquo Diabetic Medicine vol 983090983095 no 983092 pp 983092983091983089ndash983092983091983093 983090983088983089983088

[983095] M Lovestam-Adrian C Agardh A Aberg and E AgardhldquoPre-eclampsia is a potent risk actor or deterioration o retinopathy during pregnancy in type 983089 diabetic patientsrdquoDiabetic Medicine vol 983089983092 no 983089983090 pp 983089983088983093983097ndash983089983088983094983093 983089983097983097983095

[983096] C M Dibble N K Kochenour R J Worley F H yler and MSwartz ldquoEffect o pregnancy on diabetic retinopathyrdquo Obstetricsamp Gynecology vol 983093983097 no 983094 pp 983094983097983097ndash983095983088983092 983089983097983096983090

[983097] J H Price D R Hadden D B Archer and J M G HarleyldquoDiabetic retinopathy in pregnancyrdquo British Journalof Obstetricsamp Gynaecology vol 983097983089 no 983089 pp 983089983089ndash983089983095 983089983097983096983092

[983089983088] L A Owens G Avalos B Kirwan L Carmody and F DunneldquoALANIC DIP closing the loop a change in clinical practicecan improve outcomes or women with pregestational diabetesrdquoDiabetes Care vol 983091983093 no 983096 pp 983089983094983094983097ndash983089983094983095983089 983090983088983089983090

[983089983089] A M Egan M C Dennedy W Al-Ramli A Heerey G Avalosand F Dunne ldquoALANIC-DIP excessive gestational weight

gain and pregnancy outcomes in women with gestational orpregestational diabetes mellitusrdquo Journal of Clinical Endocrinol-ogy and Metabolism vol 983097983097 no 983089 pp 983090983089983090ndash983090983089983097 983090983088983089983092

[983089983090] UK National Screening Committee EssentialElementsin Devel-oping a Diabetic Retinopathy Screening Programme NationalScreening Programme or Diabetic Retinopathy Workbook 983092983091983090983088983088983097

[983089983091] American Diabetes Association ldquoStandards o medical care indiabetesmdash983090983088983089983091rdquo Diabetes Care vol 983091983094 supplement 983089 pp S983089983089ndashS983094983094 983090983088983089983091

[983089983092] NICE guidelines [CG983094983091] Diabetes in pregnancy managemento diabetes and its complications rom pre-conception to thepostnatal period 983090983088983088983096 httpwwwniceorgukguidancecg983094983091chapterguidance

[983089983093] Te Diabetes Control and Complications rial Research GroupldquoEffect o pregnancy on microvascular complications in thediabetes control and complications trialrdquo Diabetes Care vol 983090983091no 983096 pp 983089983088983096983092ndash983089983088983097983089 983090983088983088983088

[983089983094] R C emple V A Aldridge M J Sampson R H GreenwoodP J Heyburn and A Glenn ldquoImpact o pregnancy on theprogression o diabetic retinopathy in ype 983089 diabetesrdquo Diabetic Medicine vol 983089983096 no 983095 pp 983093983095983091ndash983093983095983095 983090983088983088983089

[983089983095] C S Arun and R aylor ldquoIn1047298uence o pregnancy on long-term progressiono retinopathy in patientswith type 983089 diabetesrdquoDiabetologia vol 983093983089 no 983094 pp 983089983088983092983089ndash983089983088983092983093 983090983088983088983096

[983089983096] A Hemachandra D Ellis C E Lloyd and J Orchard ldquoTein1047298uence o pregnancy on IDDMcomplicationsrdquo Diabetes Care vol 983089983096 no 983095 pp 983097983093983088ndash983097983093983092 983089983097983097983093

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 78

Journal o Diabetes Research 983095

[983089983097] Te Diabetes Control and Complications rial Research GroupldquoEarly worsening o diabetic retinopathy in the diabetes controland complications trialrdquo Archives of Ophthalmology vol 983089983089983094 no983095 pp 983096983095983092ndash983096983096983094 983089983097983097983096

[983090983088] B Rosenn M Miodovnik G Kranias et al ldquoProgression o dia-betic retinopathy in pregnancy association with hypertensionin pregnancyrdquo American Journalof Obstetrics amp Gynecology vol983089983094983094 no 983092 pp 983089983090983089983092ndash983089983090983089983096 983089983097983097983090

[983090983089] R Axer-Siegel M Hod S Fink-Cohen et al ldquoDiabeticretinopathy during pregnancyrdquo Ophthalmology vol 983089983088983091 no 983089983089pp 983089983096983089983093ndash983089983096983089983097 983089983097983097983094

[983090983090] Hellstedt R Kaaja K eramo and I Immonen ldquoTe effecto pregnancy on mild diabetic retinopathyrdquo Graefersquos Archive for Clinical and Experimental Ophthalmology vol 983090983091983093 no 983095 pp983092983091983095ndash983092983092983089 983089983097983097983095

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 88

Submit your manuscripts at

httpwwwhindawicom

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 78

Journal o Diabetes Research 983095

[983089983097] Te Diabetes Control and Complications rial Research GroupldquoEarly worsening o diabetic retinopathy in the diabetes controland complications trialrdquo Archives of Ophthalmology vol 983089983089983094 no983095 pp 983096983095983092ndash983096983096983094 983089983097983097983096

[983090983088] B Rosenn M Miodovnik G Kranias et al ldquoProgression o dia-betic retinopathy in pregnancy association with hypertensionin pregnancyrdquo American Journalof Obstetrics amp Gynecology vol983089983094983094 no 983092 pp 983089983090983089983092ndash983089983090983089983096 983089983097983097983090

[983090983089] R Axer-Siegel M Hod S Fink-Cohen et al ldquoDiabeticretinopathy during pregnancyrdquo Ophthalmology vol 983089983088983091 no 983089983089pp 983089983096983089983093ndash983089983096983089983097 983089983097983097983094

[983090983090] Hellstedt R Kaaja K eramo and I Immonen ldquoTe effecto pregnancy on mild diabetic retinopathyrdquo Graefersquos Archive for Clinical and Experimental Ophthalmology vol 983090983091983093 no 983095 pp983092983091983095ndash983092983092983089 983089983097983097983095

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 88

Submit your manuscripts at

httpwwwhindawicom

7212019 310239pdf

httpslidepdfcomreaderfull310239pdf 88

Submit your manuscripts at

httpwwwhindawicom