ppt jurnal smt iii oke

7/25/2019 Ppt Jurnal Smt III oke

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Chronic hypertension in pregnancy and

the risk of congenital malformations:

a cohort study

dr. Iman Ruansa


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Chronic hypertension is a common medicalcondition in pregnancy, and its prevalence is

rising because a larger number of parturients

are obese and of advanced maternal age

Little is known about the role of chronic

hypertension alone in conferring risk of

congenital malformation


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O!"C#I$"

% #he purpose of the study was to e&aminethe association between maternal chronic

hypertension and the risk of congenital

malformations in the offspring.


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'#()* )"'I+

% -e defined a cohort of /,012 completedpregnancies linked to infant medicalrecords using the 3edicaid 4nalytic"&tract.

% #he risk of congenital malformations wascompared between normotensive controlsand those with treated and untreatedchronic hypertension. Confounding was

addressed using propensity scorematching.


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34#"RI4L 4) 3"#5O)'

% Cohort

)erived from the 3edicaid 4nalytic e6tract73468

#he cohort is restricted to women who wereeligible for 3edicaid continuously from 9months prior to the estimated L3 monththrough 0 month postpartum.

Restricted to women with 1 days or more of

enrollment each month and without restrictedbenefits, private insurance, or certain state;specific managed care programs 7thatunderreport claims to 3468.


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Exclusion

-omen who were e&posed to known teratogenic

medications including lithium, antineoplastic

agents, retinoids, or thalidomide from the

"stimated L3 through the date of deliverybased on claims for dispensed medications

or who had an infant with an inpatient or

outpatient diagnosis code indicating the

presence of a chromosomal abnormality.

-omen who were e&posed to antihypertensive

3edications during the first trimester but who

lacked diagnosis codes indicating chronic

5ypertension because of a significant risk

of misclassifying the presence or absence

of hypertension in these patients 7becausethe women may have received the medications

for other indications

The final analytic cohort

included 878,126 pregnancies


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% Exposure

-omen without chronic hypertension

who did not receive antihypertensive medicationsin first trimester

3 Groups

-omen with chronic hypertension

who were treated with an antihypertensive medications

during first trimester

-omen with chronic hypertension

who were not treated with an antihypertensive medication

during first trimester


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4ntihypertensive e&posure during the firsttrimester was defined by a filled

prescription whose days< supply

overlapped the period from the L3 to =>

days after the L3.


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% Outcoes #he primary outcome was defined as the presence of ama?or congenital malformation in the offspring.

3a?or congenital malformations were defined based onhaving codes on 1 or more separate days in the infant

inpatient or outpatient records during the first 9 monthsof life indicating an organ;specific class of malformationsincluding central nervous system malformations@ eye,ear, neck, and face malformations@ cardiacmalformations@ respiratory malformations@ cleft palate orlip@ gastrointestinal malformations@ genitourinary

malformations@ musculoskeletal malformations@ or othermalformations.


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% Co!ariates

" groups of

potential confounders

measures ofhealth care utiliAation

maternal medications

obstetric characteristicsB

conditions

comorbid

medical conditions

maternal

demographic characteristics


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% 'tatistical 4nalyses

aseline

Characteristics

-omen -I#5O(# chronic

hypertension who did notreceive antihypertensive

medications in the first

trimester

-omen with C5ROIC5*"R#"'IO who were

e&posed to an antihypertensive

medication during the first

trimester

-omen with C5ROIC

5*"R#"'IO who were not

treated with an ntihypertensive

during the first trimester

Controls

(ntreated

chronic

hypertension

#reated

chronic

hypertension


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% 'ensitivity and e&ploratory analyses

Controls vs sub?ectstreated for chronic

hypertension

Controls vs untreatedchronic hypertension

freuency and unad?usted

odds ratio 7OR8 and =DE

confidence intervals 7CIs8

Logistic regression model


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% #ensiti!ity and exploratory analysesecause diabetes is such a strong risk factor

for congenital and the possibility e&ists thatthere may be residual confounding, evenad?usting for the presence of diabetes e&cluding patients with any codes ormedications indicating the presence of diabetes,=9/ patients e&cluded

'econd sensitivity analysis e&cluding patientswith preterm delivery =,>F= patientse&cluded


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R"'(L#

% 4fter matching, compared with normotensivecontrols,pregnancies complicated by treated chronichypertension were at increased risk of congenitalmalformations 7odds ratio GORH, 0.9@ =DE confidenceinterval GCIH, 0.1e0.D8, as were pregnancies withuntreated chronic hypertension 7OR 0.1@ =DE CI,0.0e0.98.

% In our analysis of organ;specific malformations, bothtreated and untreated chronic hypertension wasassociated with a significant increase in the risk of

cardiac malformations 7OR, 0.2@ =DE CI, 0.Fe0.=and OR, 0.D@ =DE CI, 0.9e0./, respectively8.% #hese associations persisted across a range of

sensitivity analyses.


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% Ta$le 1 %aseline characteristics of study patients&ithout chronic hypertension Treated chronic

hypertensi!es'nreated chronichypertensi!es

#otal D,99/ 9>/ 00,F1

4ge group, y

0= 1D2,=/9 71=.=8 F>1 7F.8 1>29 708 1>;1F 9>,0F> 79D.=8 0D9= 70.D8 9F9D 71=.=

1D;1= 0/9,1=0 71>.18 19=2 71.8 1=D 71D.8

9>;9F /,/10 7=.18 11>0 712.D8 0/=F 70D.28

9D;9= 99,=/ 7F8 0920 702.F8 =F= 7.98

JF> /11D 7>.8 F> 7F.=8 19 71.D8

RaceBethnicity

-hite, non;5ispanic 9F=,92= 7F>./8 12F 791.98 F909 79/.28

lack, non;5ispanic 1=,2/ 799.8 F99/ 7D1.18 D0/= 7FD.08

5ispanic 090,>D/ 70D.98 2= 7.98 000> 7=./8

4sian 1=,20 79.D8 0D 71.18 1D/ 71.18

Other F0,>9= 7F.8 1F 798 F>1 79.D8

(nknown 0/,91F 71.>8 02F 71.>8 110 70.=8

atients characteristics

ree&isting )3 99,2=F 79.=8 0== 719.=8 022= 70F.D8

+estational )3 2/,>0 7/.8 1011 71D.D8 1102 70=.98

Chronic renal disease =921 70.08 F>F 7F.=8 D0/ 7F.D8

#obacco use /0,102 7.98 220 7.>8 0>>/ 7.8

3edication e&posure

Insulin 0D,2F 70.8 09F9 702.18 0>>D 7.8

Oral diabetes medications 02,21 70.=8 1>F1 71F.28 0>0> 7.8


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% Ta$le 2 %aseline characteristics of study patients after propensity score atching(Characteristic Coparison 1 Coparison 2

-ithout chronichypertension

#reated chronichypertension

-ithout chronichypertension

#reated chronichypertension

#otal 19,F1/ />= 9F,F9F 00,F/

4ge group, y

0= 0>1 7F.28 F>1 7D.18 2>2= 70/.28 1>29 708

1>;1F FD=> 70=.28 0D91 70=.28 0>,0D 71=.28 9F9F 71=.=8

1D;1= 2=20 71=./8 1911 71=./8 =>F 712.F8 1=D/ 71D.8

9>;9F 20/ 712.F8 1>>2 71D./8 D92= 70D.28 0/=9 70D.28

9D;9= 9D29 70D.18 00/ 70D.18 1== 7.F8 =F 7.98

JF> 0>D9 7F.D8 92> 7F.28 1 71.F8 19 71.D8

RaceBethnicity

-hite, non;5ispanic /== 79F.08 1DD 799.08 09,921 79.8 F909 79/.28

lack, non;5ispanic 00,/=9 7D>.98 9=2/ 7D>.8 0D,F1D 7FF.8 D0/D 7FD.08

5ispanic 1>1D 7.28 2// 7./8 91>D 7=.98 000> 7=./8

4sian F0 71.08 0D 71.F8 29= 70.=8 1D/ 71.18

Other 2=1 7908 1F0 79.08 0D/ 79.F8 F>1 79.D8

(nknown FF/ 70.=8 0DF 718 2F2 70.=8 110 70.=8


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atients characteristics

ree&isting )3 F9/D 70./8 0DD9 70=.=8 F/ 709.=8 022D 70F.D8

+estational )3 DFD 719.98 0/0 711.8 229= 70=.98 110F 70=.98

Chronic renal disease =2 7F.18 90= 7F.08 0F>1 7F.08 D0F 7F.D8

#obacco use 01/ 7/.8 291 7.08 1==1 7./8 0>>/ 7.8

3edication e&posure

Insulin 12/1 700.F8 =2 701.28 1F9 7.98 0>>0 7./8

Oral diabetesmedications

92= 70D.8 09= 70/.=8 1292 7/./8 0>>2 7.8


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% Ta$le 3 The association $et)een chronic hypertension *treated and

untreated+ and congenital alforations copared

% )ith norotensi!e controlsCharacteristics Treated chronic hypertension 'nreated chronic hypertension

(nad?usted ' matched (nad?usted ' matched

Composite congenitalmalformations

0./ 70.2K0.=8 0.9 70.1K0.D8 0.D 70.FK0.28 0.1 70.0K0.98

Organ; specific malformations

Central nervoussystem malformations

1.> 70.9K98 0.F 7>.K1.98 0.F 7>.=K1.08 0.1 7>./K0.=8

3alformations of theeye, ear, neck, or face

>.= 7>.DK0./8 >. 7>.FK0.8 0.0 7>./K0.=8 0.1 7>./K1.08

Cardiac malformations 1.2 71.9K98 0.2 70.FK0.=8 1.0 70.=K1.98 0.D 70.9K0./8

Respiratory malformations 0. 70.1K1./8 0.D 7>.=K1.F8 0.F 7>.=K18 0.9 7>.K1.08

Cleft palate and lip 0.9 7>./K1.98 0.9 7>.2K1.28 0.0 7>./K0.=8 0.0 7>.2K1.08

+astrointestinal malformations 0.0 7>.K0.D8 0.> 7>./K0.D8 0.0 7>.=K0.F8 0.> 7>./K0.98

+enitourinary malformations 0.F 70.0K0.8 0.0 7>.K0.D8 0.9 70.0K0./8 0.0 7>.=K0.D8

3usculoskeletal malformations 0.0 7>.=K0.F8 >.= 7>./K0.18 0.> 7>.K0.18 >. 7>./K0.08

Other malformations 0. 70.9K1.F8 0.2 70.0K1.98 0.0 7>.K0.D8 0.> 7>./K0.F8


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% Ta$le #ensiti!ity and exploratory analyses

Characteristic Treated chronic hypertension 'ntreated chronic hypertension

'ensitivity analysis 0, e&cluding )3,

+)3, insulin, and diabetes medication Composite congenital malformations 0.1 70.>K0.F8 0.1 70.0K0.98

Cardiac malformations 0.D 70.1K0.8 0.D 70.1K0./8

'ensitivity analysis 1, e&cluding pretermdeliveries

Composite congenital malformations 0.9 70.0K0.28 0.0 70.>K0.98

Cardiac malformations 0.D 70.1K0.=8 0.0 7>.=K0.F8

'ensitivity analysis 9 7all covariatesdefined based on trimester 08

Composite congenital malformations 0.9 70.1K0.28 0.1 7>.=K0.28

Cardiac malformations 0.2 70.9K0.=8 0.9 7>.=K0.=8

'ensitivity analysis F 7outcome definedby a single diagnostic code in the infantrecord8

Composite congenital malformations 0.1 70.0K0.98 0.1 70.0K0.98

Cardiac malformations 0.F 70.9K0.28 0.D 70.9K0.28


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"&ploratory analysis of specific cardiacmalformations

$entricular septal defect 0.F 70.>K1.>8 0.0 7>.K0.D8

Right ventricular septal defect 0.1 7>.1K2.18 0.9 7>.FK9.D8

'ingle ventricle 9.> 7>.FK10.98 F.D 7>.K12.=8

'ecundum atrial septal defect 0.D 70.>K1.F8 0.9 7>.=K0.=8

Conotruncal defect 0./ 7>.K9.D8 >.= 7>.FK0.8

Left ventricular outflow obstruction 0. 7>.KF.08 0.0 7>.DK1.18


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CO33"#

% #here are few studies that have e&ploredthe role of hypertension in conferringrisk of

congenital malformations in the offspring.

% Our findings confirm and e&tend theseobservations from previous studies.


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%irst, we e&amined the role specifically ofchronic hypertension in conferring the risk of

malformations, whereas prior studies e&amined

all pregnancy;related hypertensive disorders

together.% 'econd, our study e&amined a full range of

organ;specific congenital malformations in

relation to hypertension, finding that chronic

hypertension is associated most strongly withcardiac malformations.


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%#hird, our study carefully controlled for a widerange of potential confounders of the association

between chronic hypertension and congenital

malformations including comorbid conditions as

well as other relevant medication e&posures andmarkers of overall health status and health care

utiliAation.

% inally, the large siAe of our cohort allowed us to

make relatively precise estimates with regard tothe risk of malformations associated with treated

and untreated hypertension.


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% 4lthough we were careful to identify potential

confounders of the association between chronic

hypertension and malformations using maternal

inpatient and outpatient diagnostic claims,

medications, and health care utiliAation variables, it

remains possible that residual bias is present

because of unmeasured or unknown confounders.

% Our study also cannot directly address whether

treatment of chronic hypertension in pregnancy willdecrease the risk of malformations.


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% 4lthough the estimate of risk of malformations

was similar for both treated and untreated

chronic hypertension, our study cannot e&clude

the possibility that certain antihypertensives are

teratogenic.% 4s in all observational studies, we cannot

e&clude the possibility of residual confounding

and additional studies replicating these findings

are necessary before chronic hypertensionshould be considered an established risk factor

for congenital malformations.


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COCL('IO

% #here is a similar increase in the risk ofcongenital malformations 7particularly cardiacmalformations8 associated with treated anduntreated chronic hypertension that isindependent of measured confounders.

% 'tudies evaluating the teratogenic potential ofantihypertensive medications must control forconfounding by indication.

% etuses and neonates of mothers with chronic

hypertension should be carefully evaluated forpotential malformations, particularly cardiacdefects.


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CRI#IC4L 4R4I'4L-uestions .ns)ers Explanation

0. 'tudy design,

survey or registrationM

'urvey #he control group consisted of /F

healthy pregnant women and =>patients with diagnosed pre;eclampsia.#otal R4 was isolated from placentaand the mR4 level of e&amined geneswas to determine using real;time CR.

1. Inductive ordeductive reasoningM

)eductive7theory Nprediction Nobservation Nconclusions8

#heory: -riters e&plained the theory ofchronic hypertension in coferring risk ofcongenital malformation.rediction: Chronic hypertension alonemay be related to development ofcongenital malformation in the

offspring.Conclusions: #here is a similarincrease in the risk of congenitalmalformations associated with treatedand untreated chronic hypertension.


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-uestions .ns)ers Explanation

9 and F #ype andscales of eachvariables in this study

)ependent variables: Chronichypertension 7nominal8 and congenitalmalformation 7nominal8

Independent $ariables:4ge 7ratio8RaceBethnicity 7nominal8atient characteristics 7nominal83edication e&posure 7nominal8

D. #ype of data,primary, secondary or

tertiary resourcesM

'econdary )ata was derived from 3edicaid4nalytic e6tract 73468

2. +roup or ungroupdataM

+roup


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/. 4d hoc or routinedataM

4d hoc )ata was collected for some period oftime during study

. 3easures of Central

#endency, ositionand )ispersion

ot

mentioned

=. #ables that wasused to present resultsof this study

reuencytables

'ee page D,2, / and

0>. +raph used in thispaper

'catter;plot 'ee page =


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CRI#IC4L 4R4I'4L


00. uality of researchdata

5igh uality 0. (sed primary data1. +ood operational definition9. (sing valid measurement techniue

01. ias Low risk of

bias

4lmost all known confounding

factors was controlled

09. 'ample siAecalculation for thisstudy

otmentioned

0F. 'amplingtechniue

#otalsampling

4ll studies that met inclusion ande&clusion criteria were included inthis study


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0D and 02. 'tatisticalanalysis

ivariateanalysis: one;way 4O$4test tocomparemean values

#he e&perimental data were analyAedusing the ''' 0/.> for -indowssoftware. 3ean values were comparedby one;way 4O$4 test. #he value of pP >.>D was considered as statisticallysignificant.

0/. "rror to concludestatistical analysisresults

one

0. 5ow was the

presentation of resultsin this paperM

+ood -riters clearly e&plained

background, methods and results inthis study. #hey compare resultswith another study and e&plainlimitation of this study


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