cocaína e gestação revisão 2010

8/3/2019 cocaína e gestação revisão 2010

http://slidepdf.com/reader/full/cocaina-e-gestacao-revisao-2010 1/12

OBSTETRICS

Effects of cocaine use during pregnancy on low birthweightand preterm birth: systematic review and metaanalysesKaty Gouin, MD, FRCSC; Kellie Murphy, MD, FRCSC; Prakesh S. Shah, MRCPCH, FRCPC;and the Knowledge Synthesis group on Determinants of Low Birth Weight and Preterm Births

OBJECTIVE:To review systematically maternal antenatal cocaine ex-posure and adverse perinatal outcomes.

STUDY DESIGN:Medline, Embase, CINAHL and secondary referencesin relevant studies were searched. English language studies of antena-tal cocaine exposure and pregnancy outcomes published from 1966 toJuly 2009 were included. Metaanalyses were performed using the ran-dom effects model.

RESULTS:Thirty-one studies were included. Cocaine use during preg-

nancy was associated with signicantly higher odds of preterm birth(odds ratio [OR], 3.38; 95% condence interval [CI], 2.72–4.21), low

birthweight (OR, 3.66; 95% CI, 2.90–4.63), and small for gestationalage infants (OR, 3.23; 95% CI, 2.43–4.30), as well as shorter gesta-tional age at delivery ( 1.47 week; 95% CI, 1.97 to 0.98 week)and reduced birthweight ( 492 g; 95% CI, 562 to 421 g).

CONCLUSION:Prenatal cocaine exposure is signicantly associatedwith preterm birth, low birthweight, and small for gestational ageinfants.

Key words : birthweight, cocaine, gestational age, pregnancy,prematurity

Cite this article as: Gouin K, Murphy K, Shah PS, et al. Effects of cocaine use during pregnancy on low birthweight and preterm birth: systematic review andmetaanalyses. Am J Obstet Gynecol 2011;204:x-ex-x-ex.

Birthweight (BW) and gestationalage (GA) at birth are important de-

terminants of perinatal, neonatal, child-hood, and adult health. 1 Factors thoughtto be associated with low birthweight(LBW)andpretermbirth (PTB) include,butarenot limited to maternal,paternal,fetal, societal, environmental, life style-related, infectious, nutritional, genetic,and psychosocial factors. An associationbetween maternal antenatal use of co-caine and adverse pregnancy outcome

has been suggested. The high prevalenceof cocaine use during pregnancy has be-come a major health concern. Approxi-mately 15-17% of regular users of co-caine are women of childbearing age. 2

Cocaine is a central nervous systemstim-ulant. Because of its sympathomimetic-driven vasoconstrictive effects, it canlead to hypertension in the mother andfetus, which may result in placental in-farcts or hemorrhages at any time ingestation. 3 Because of its high water

content, lipid solubility, low molecularweight, and lowionization at physiologicpH, cocaine is believed to cross the pla-cental barrier by simple diffusion. 4 Ex-posure to cocaine has been reported tobe associated with a shorter gestation,premature birth, abruptio placenta, andother adverse maternal and neonataloutcomes. 3

Reports of fetal cocaine effects havebeen controversial, as the interpretationof results is hampered by the fact thatcocaine use is commonly accompaniedby other confounding maternal lifestylefactors. Some of these confounding fac-tors include cigarette smoking, otherdruguse(heroin,cannabis,methadone,al-cohol, and others), lower socioeconomicstatus, and lack of adequate prenatal care,all of which may combine to contribute topoor pregnancy outcome. Therefore, webelievethat a thorough and currentreviewof the literature will help elucidate andquantify the effects of maternal antenatalcocaineuseonperinatal outcomes thereby providing up-to-date information. Ourobjective was to review systematically theeffect of cocaine consumption duringpregnancy on various neonatal outcomes

(LBW, PTB, and small-for-gestational age[SGA] neonates).

From theDivision of Maternal-Fetal Medicine,Department of Obstetrics and Gynecology (Drs Gouin andMurphy), Mount Sinai Hospital; CentreHospitalier Universitaire de Québec(Dr Gouin), Université Laval, Québec city, Québec; and theDepartments of Obstetrics andGynecology (DrMurphy) and Pediatrics andHealthPolicy, Management and Evaluation (Dr

Shah), University of Toronto, and theDepartment of Pediatrics (DrShah), Mount SinaiHospital, Toronto, Ontario, Canada.Presented as a poster at the Annual Meeting of Canadian Pediatric Society,Vancouver,Canada,June 22-26, 2010.Received July 2, 2010; revised Sept. 22, 2010; accepted Nov. 2, 2010.Reprints: Katy Gouin, MD, FRCSC, Department of Obstetrics and Gynecology, Centre HospitalierUniversitaire de Québec, CHUL, CME, 2705, Boulevard Laurier, Québec, Québec, Canada, G1V4G2. [email protected]. This study was supported by funding from the Canadian Institute of Health Research (CIHR)Knowledge Synthesis/Translation Grant no. KRS 86242. CIHR played no role in analyses, writingof the report, interpretationof data, or decision to submit the manuscript.Members of the Knowledge Synthesis Group on determinants of LBW/preterm births are listed atthe end of this full-length article.

0002-9378/$36.00 • © 2011 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2010.11.013

Research www.AJOG.org

MONTH 2011 American Journal of Obstetrics & Gynecology 1.e1

mailto:[email protected]





TABLE 1Summary of included studies of cocaine exposure and pregnancy outcomes

AuthorYear ofstudy Type of study Setting of study Population

Exposureassessment(when, how)

Outcomesassessed

Confoundersadjusted for Results

Qualityassessment(risk ofbias)

Bingol et al4

1984-85 Prospective cohort withunmatched controls(similar for MA, SES,tobacco, ethnicity)

2 large inner cityhospitals in New York City(Harlem, Bronx)

Poor inner citywomen at delivery Neonate urine atbirth PTD, BW Low

................................................................................................................................................................................................................................................................................................................................................................................

MacGregor et al15 1983-86 Retrospective cohortwith matched controls(MA, parity, SES,tobacco, medcomplications)

Single center,Chicago

Pregnant womenreceiving care atthe Perinatal Centerfor ChemicalDependence ofNorthwesternUniversity

NS? Maternal self-reportantenatally

LBW, PTD,SGA, BW,GA

Low

................................................................................................................................................................................................................................................................................................................................................................................

Cherukuri et al16 1986 Retrospective cohortwith matched controls(MA, parity, PNC, SES,race, ROH)

Single centerBrooklyn NYC

Patient delivering atKings CountyHospital, on publicassistance

Maternal self-report atdelivery

LBW, PTD,SGA, BW,GA

Low

................................................................................................................................................................................................................................................................................................................................................................................

Chouteau et al17 1986 Retrospective cohort

with unmatchedcontrols

Single center,

large teachinghospital, NYC

Pregnant at L D

who did not receive ANC

Maternal urine

toxicology atadmission

BW, GA Low

................................................................................................................................................................................................................................................................................................................................................................................

Fulroth et al18 NS Prospective cohort withunmatched controls

Single center,Oakland

All infants deliveredat Highland GeneralHospital, Oakland

Maternal self-report or urineat admissionand neonateurine

PTB Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Hadeed, Siegel19 1984-87 Prospective cohort withmatched controls (MA,parity, tobacco, SES,ethnicity)

Single center,HollywoodPresbyterianCenter in Los Angeles,California

Pregnant womenreceivinggovernmentsubsidized medicalcare

Maternal andinfant urineimmediatelyafter birth

BW, GA Low

................................................................................................................................................................................................................................................................................................................................................................................

Little et al20 1987 Retrospective cohortwith unmatchedcontrols

Single center,Dallas, Texas

Mother of infantborn at ParklandMemorial Hospital

Self-report (SW)and chart review

PTD, SGA,BW, GA

Low

................................................................................................................................................................................................................................................................................................................................................................................Neerhof et al21 1986-88 Prospective cohort with

unmatched controlsSingle center,Chicago

All patientsadmitted to L D(screening policy)

Maternal urineat admissionand neonateurine

PTD, SGA,BW, GA

Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Zuckerman et al22 1984-87 Prospective cohort withunmatched controls

Single center,Boston

Recruited atwomen’s andadolescent prenatalclinic (52%Medicaid, lowincome)

Interview andmaternal urineantenatally andPP

BW, GA Low

................................................................................................................................................................................................................................................................................................................................................................................

Gillogley et al23 1987-88 Retrospective cohortwith matched controls(race, discharge date)

Single center,Perinatal unit,University ofCalifornia, Davis,Sacramento

Admission Observice of UCDMC,urban, 93%Medicaid or noinsurance, diverseethnicity (routinetesting)

Maternal urineat admissionneonate urine

LBW, PTB,BW, GA

Multiple regressionwith smoking

129g associatedwith tobacco use

Low

................................................................................................................................................................................................................................................................................................................................................................................

Calhoun, Watson24 1987-88 Prospective cohort withmatched controls(parity, SES, MA)

Single center,L D, Portland

Indigent, low rate of ANC, no insurance,

Maternal andinfant urine atadmission

PTB, SGA,BW, GA

Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Cohen et al25 1986-87 Retrospective cohortwith matched controls(MA, race, parity)

Single center,San FranciscoGeneral hospital

Toxic screen fromL D or nursery,88% black

Maternal and/orneonatal urine atadmission

LBW, PTB,BW, GA

Minimal

................................................................................................................................................................................................................................................................................................................................................................................

Kelley et al26 NS Retrospective cohortwith controls matched(age of infant, race,sex, SES)

Single center,pediatric well-child clinic, largeurban teachinghospital, Boston

Infant 1wk-26 mo,80% black, 96%Medicaid

Maternal self-report atdelivery orneonate urine

LBW, PTB,SGA, BW,GA

Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Gouin. Cocaine use during pregnancy on low birthweight and preterm birth. Am J Obstet Gynecol 2011. (continued )

Research Obstetrics www.AJOG.org

1.e2 American Journal of Obstetrics & Gynecology MONTH 2011



TABLE 1Summary of included studies of cocaine exposure and pregnancy outcomes (continued)



Outcomesassessed



McCalla et al27

1988-89 Cross-sectional cohortwith unmatchedcontrols

Single center,municipalhospital, NYC

Inner-city Mate rnal u rineat admissionneonate urine

LBW, GA Regressionanalysis for: PNC,MA, parity,tobacco, ROH

For smoking,125.0g (P .04)for BW and 0.37wks (P .18) for GA

Low

................................................................................................................................................................................................................................................................................................................................................................................

Richardson, Day28 1983-86 Prospective cohort withunmatched controls

Single center,Magee-WomensHospital,interview eachtrimester

Young, single, lowincome womenattending publicprenatal clinic

Maternal self-reportantenatally

BW, GA,LBW, SGA

Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Spence et al29 NS Prospective cohort withunmatched controls

Single center,HahnemannUniversityHospital,Philadelphia

Consecutiveadmission in L D,routine screen

Maternal urineat delivery

PTB, BW Low

................................................................................................................................................................................................................................................................................................................................................................................

Bateman, et al30 1985-86 Prospective cohort withunmatched controls

Single center,Harlem Hospital,

NYC

Innercity Maternal self-report or infant

urine

LBW, PTB,BW, GA

GA, MA, gravidity,race, sex, PNC,

syphilis, tobacco,ROH, marijuana,PCP, opiates

Regression coefcient121g (P .005)

Low

................................................................................................................................................................................................................................................................................................................................................................................

Forman et al31 1990-91 Prospective cohort withunmatched controls

3 centers,Toronto

Mother-infant pairsin 3 nurseries, 69%white

Neonate urineand hairs

BW Tobacco - LBWBW

LBW: 50% of smokersvs 8% of nonsmokers2899 750g (C T)3423 612g (C only)3414 564 (No exp)

Low

................................................................................................................................................................................................................................................................................................................................................................................

Rosengren et al32 1990 Prospective cohort withunmatched controls

2 urban centers,Hartford,Connecticut

Consecutivenewborns, urbanand suburbanpopulation

Neonatemeconium

LBW, PTB,BW

Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Eyler et al33 1987-88 Retrospective cohortwith matched controls(race, MA, parity, GA atPNC, ROH, tobacco)

Single center,regional hospital(referral center),Florida

Women using ruralcounty public healthunit (min accessrehab), Medicaid,low income

Maternal historyor urine orneonate urine

LBW, PTB,GA, BW

Low

................................................................................................................................................................................................................................................................................................................................................................................

Kliegman et al34 1990-91 Prospective cohort withunmatched controls

Single center,large urbanuniversity-basedmaternityhospital,Cleveland

Anonymous screen,unselectedpopulation

Maternal urineat delivery orpostpartum

LBW, PTD Race, MA, ROH,marijuana,tobacco, PNC,primiparous,history of PTB

Multivariate logisticmodels adjusted OR,9.90 (0.53-1.84)

Low

................................................................................................................................................................................................................................................................................................................................................................................

Neuspiel et al35 1992 Retrospective cohortwith unmatchedcontrols

Single center,public hospital,Bronx, NYC

NS Maternal urineat admissionand neonatecord blood

BW, GA Cotinine, smokinghistory

204g (P .15 ) Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Singer et al36 NS Retrospective cohortwith matched controls(race, SES)

NS AA, low SES, publicassistance

Maternal urineand self-reportantenatally

LBW, BW,GA

Low

................................................................................................................................................................................................................................................................................................................................................................................

Miller et al37 1990 Retrospective cohortwith matched controls(race, age, parity,month of delivery)

Single center,New Orleans

Large urban center,innercity, indigentpopulation

Maternal urineat delivery

BW, GA,PTB, SGA

TobaccoPNC

BW/Tobacco :2759462 (45) for

cocaine vs 2824876 (75) for controlsBW/Tobacco –:3051

602 (17) forcocaine vs 3078853 (167) for controlsGA/Tobacco : 38.4

2.5 (45) for cocainevs 37.6 4.4 (75) forcontrolsGA/Tobacco-: 39.01.6 (16) for cocaine vs38.4 4.3 (164) forcontrols

Minimal

................................................................................................................................................................................................................................................................................................................................................................................

Gouin. Cocaine use during pregnancy on low birthweight and preterm birth. Am J Obstet Gynecol 2011. (continued )

www.AJOG.org Obstetrics Research




M ATERIALS AND M ETHODS

The Meta-analysis of Observational

Studies in Epidemiology (MOOSE) cri-teria were followedforthis systematicre-view.5 The methods of review by ou rgroup have been described previously. 6

The medical literature published be-tween 1966 through July 2009 wassearched in Medline, Embase, CINAHLdatabases, and bibliographies of identi-ed articles for papers reporting on ges-tational cocaine exposureand pregnancy outcome. A search strategy using acombination of “pregnancy,” “cocaine,”

“preterm birth,” “premature,” “intra-uterine growth restriction,” “low birth-

weight,” “small-for-gestational age,”“birthweight,” “gestational age,” “out-

come,” “complications,”“intervention,”and “cessation” keywords (MeSH) wasused. Retrieved articles were handsearched for additional references. Non-English papers, comments, letters, edito-rials, and reviews were excluded. How-ever, references of excluded publicationswere searched.

English language studies reporting oncocaine exposure in pregnancy and out-comes of interest: LBW (dened as BW

2500 g), PTB (dened as birth before

37 completed weeks of gestation), SGA(dened as BW 10th percentile for

GA), BW in grams, and GA in weekswere reviewed. The criteria for inclusion

of articles were as follows: human expo-sure to any amount of cocaine duringany or all the trimesters of pregnancy, asevidenced by drug history, maternal orneonate urine test or neonate meconiumtest, andreportof pregnancyoutcome of interest. Prospective and retrospectivecohort studies, as well as case-controlstudies of cocaine exposure were in-cluded. Polydrug use is common in thispopulation andwasnotan exclusioncri-terion. We excluded studies that re-

ported duplicate populations, exposurethat was ambiguous and those that did

TABLE 1Summary of included studies of cocaine exposure and pregnancy outcomes (continued)



Outcomesassessed



Shiono et al38

1984-89 Prospective cohort withunmatched controls Multicenter (7centers)university-basedprenatal clinicsin US (Oklahoma,Louisiana, Texas,Tulane,Washington,Harlem)

Multiethnic, from Vaginal Infectionsand Prematuritystudy

Maternal serumor self-reportantenatally or atdelivery

LBW, PTB Frequency useBloodconcentrationTobaccoROHMarijuana

Logistic regression forsmoking LBW OR, 1.1(0.6-2.2) PTB OR, 1.5(0.9-2.6)

Low

................................................................................................................................................................................................................................................................................................................................................................................

Kistin et al39 1988 Retrospective cohortwith unmatchedcontrols

Multicenter (12centers) UnivIllinois hospitalperinatalnetwork

Patient delivering ina hospital of thenetwork

Self-report ormaternal orneonate urine atdelivery

LBW, PTB,SGA

Race AgeGravidity

Low

................................................................................................................................................................................................................................................................................................................................................................................

Sprauve et al40 1992 Retrospective cohortwith unmatchedcontrols

Single center, Atlanta

Innercity, indigent,routine voluntaryurine drugscreening

Maternal urineat any timeduringpregnancy orwithin 1 wk ofdelivery

LBW, PTD,SGA

ROH, tobacco,weight, age, PNC,PTB

LBW: 1.59 (1.03-2.43)PTB: 0.88 (0.63-1.22)SGA: 1.7 (1.24-2.32)

Low

................................................................................................................................................................................................................................................................................................................................................................................

Richardson et al41 1988-93 Prospective cohort withunmatched contols

Single center,PNC clinicMagee-Women’shospital,Pittsburgh

Innercity, lowincome

Maternal self-reportantenatally andPP

PTB, LBW,SGA

PNC Low

................................................................................................................................................................................................................................................................................................................................................................................

Bandstra et al42 1990-93 Retro and prospectivecohort with unmatchedcontrols

Single center,Miami prenatalcocaine study

AA, innercity, lowSES

Maternal self-report and urine,infant urine andmeconium

LBW, BW,GA

Tobacco BW 0.006 ( 0.012-0.000) P .038 GA 0.008 (0.002-0.014)P .10

Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Ogunyemi,Hernandez-Loera43

1991-2000

Retrospective cohortwith matched controls

Single center,Los Angeles

All deliveries at thisinstitution

Maternaltoxicologyscreen PP

BW, GA,PTB, SGA

Tobacco PTB coefcientregression0.045(0.06) ( 0.08 to

0.17)

Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Bada et al44 NS Retrospective cohortwith unmatchedcontrols

Multicenter (4centers)Providence,Miami, Memphis,Detroit

Database MaternalLifestyle Study

Maternal self-report orneonatemeconium

LBW, PTB,SGA

Tobacco LBW 5.57 (3.06 -7.91)PTB 3.66 (0.87-6.53)SGA 13.79 (10.08-17.33)

Low

................................................................................................................................................................................................................................................................................................................................................................................ AA,African American;ANC , antenatal care;BW , birthweight;exp , exposure;GA,gestational age;L D , labor and delivery suites;LBW,low birthweight;MA, maternal age;NS , not specied;Ob ,obstetrics;PNC , prenatal care;PP , postpartum;PTB , preterm birth;PTD , preterm delivery;ROH , alcohol;SES , socioeconomic status;SGA,small for gestational age;UCDMC , University of CaliforniaDavis Medical Center.

Gouin. Cocaine use during pregnancyon low birthweight and preterm birth. Am J Obstet Gynecol 2011.





not report on the outcomes of interest.Studies fullling all inclusion criteriawere included for detailed review. Tworeviewers (K.G. and K.M.) indepen-dently assessed eligibility, risk of bias,and extracted information using prede-

termined standardized data collectionforms. Risk of bias for observationalstudies was evaluated using criteria forselection bias, exposure assessment bias,confounder adjustment, analytic bias,outcome assessment bias, and attritionbias according to our previously re-ported criteria 6 (Appendix 1).

The third reviewer (P.S.) acted as an ar-bitrator. Metaanalyseswere performedus-ing the random effects model and unadjusted odds ratio (OR) or weighted mean

difference and 95% condence interval(CI). A priori planned sensitivityandsub-group analyses were planned for recentpublications vs older publications, divid-ing studies into 2 equal divisions based on year of publication (before or after 1991),whether objective vs self-reported use of cocaineexposurewasreported in thestud-ies, whether study was prospective or ret-rospective, whether studies had minimal/low risk of overall bias compared withstudies with moderate risk of biases andwhether matched or unmatched controlswere used for analyses. Clinical heteroge-neitywas assessedandreported inthetableof included studies ( Table 1). Statisticalheterogeneity was assessed using theI-squared (I 2 ) values.7

R ESULTS

Assessment of effectsof cocaine exposureFour hundred seventy-seven citationswere identied. After review, 55 reportswere retrieved for detailed evaluation.Thirty-one studies met inclusion criteriaand were included in this systematic re-view (Figure 1). Characteristics of in-cluded studies are described in Table 1.The risk of bias and quality of the studiesare reported in Appendix 2.1. LBW: cocaine use during pregnancy

wassignicantly associatedwithLBWbirths as compared with women who

didnot usecocaine during pregnancy (19 studies, 38,796 participants, un-

adjusted pooled OR, 3.66; 95% CI,2.90–4.63; I2 72%) (Figure 2).

2. PTB: when compared with nonusers,cocaine use during pregnancy wassignicantly associated with PTB be-

fore 37 weeks (24 studies, 39,860participants, unadjusted pooled OR,3.38; 95% CI, 2.72–4.21; I2 73%)(Figure 3).

3. SGA: cocaine use during pregnancy vs no use was signicantly associatedwith SGA (14 studies, 28,098 partici-pants, unadjusted pooled OR, 3.23;95% CI, 2.43–4.30; I2 87%) (Fig-ure 4).

4. GA: cocaine use during pregnancy vsno use was associated with an earlier

gestational age at birth (13 studies,4272 participants; 1.47 weeks; 95%

CI, 1.97 to 0.98 weeks; I2 87%)(Figure 5).

5. BW:Cocaineuseduring pregnancyvsno use was associated with LBW (18studies, 6855 participants; 492g;

95% CI, 562 to 421 grams; I2

71%) (Figure 6).

Subgroup analysesA priori planned sensitivity and sub-group analyses were performed ( Table2). The results did not differ when earlierstudies were compared with later studieswhether objective or self-reported as-sessment of cocaine exposure were re-ported in the studies, whether study wasprospective or retrospective, whether

studies had minimal/low risk of overallbias compared with studies with moder-

FIGURE 1Literature search owchart

Initial citations identified (n = 477)

Citations excluded (n = 422)Reasons:

Citations abstracted for detailed evaluations (n = 55)

Studies included in the systematic review (n = 31)

Data included in metaanalysis1. Low birthweight (n = 19)2. Preterm birth (n = 24)3. SGA (n = 14)4. Birthweight (n = 18)5. Gestational age (n = 13)

1. No outcome data2. Not a RCT, cohort, or casecontrolled trial3. Cocaine not main drug used4. Only polydrug use reported

Excluded after full review (n = 29)1. Data included in other studies(n = 4)2. No data on outcome of interest(n = 14)3. Control not defined (6)4. Data unextractable (5)

Studies identified from hand searching (n = 5)

RCT , randomized controlled trial;SGA, small for gestational age.

Gouin. Cocaine use during pregnancyon lowbirthweight and preterm birth. Am J Obstet Gynecol 2011.



http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-

http://-/?-



FIGURE 2Effect of antenatal cocaine exposure on LBW ( < 2500 g)

Study or subgroup

MacGregor 1987Cherukuri 1988Chouteau 1988Gillogley 1990Richardson 1991Cohen 1991McCalla 1991Kelley 1991Bateman 1993Rosengren 1993Kliegman, 1994Eyler 1994Singer 1994Shiono, 1995Kistin 1996Sprauve 1997Richardson 1999Bandstra 2001Bada 2005

Total (95% CI)

Total eventsHeterogeneity: Tau² = 0.14; Chi² = 64.25, df = 18 ( P < .00001); I² = 72%Test for overall effect: Z = 10.84 ( P < .00001)

Events8

214332

3315210

11154

47331218

1511837

465

1101

Total2455

124139

3483

12830

3612113

168100175

64483

62253

1072

3389

Events37

231445

9118

23843223014

591756470

254

1567

3781

Total7055

218293600166983

30387600227168100

729513043

3158302147

7565

35407

Weight2.1%3.7%6.3%5.5%2.7%4.6%7.7%1.7%7.7%3.3%2.6%6.7%5.3%6.1%6.4%9.2%5.4%3.3%9.7%

100.0%

M-H, Random, 95% CI11.17 [2.66, 46.88]

4.24 [1.62, 11.08]4.50 [2.55, 7.95]

5.96 [3.06, 11.61]1.19 [0.35, 4.06]

10.40 [4.65, 23.28]5.02 [3.36, 7.50]

7.00 [1.38, 35.48]4.08 [2.73, 6.10]

4.05 [1.42, 11.58]4.14 [1.18, 14.56]

1.79 [1.06, 3.00]3.03 [1.50, 6.10]0.84 [0.46, 1.51]

6.36 [3.67, 11.02]2.60 [2.10, 3.23]4.53 [2.29, 8.99]

6.12 [2.14, 17.55]2.93 [2.57, 3.35]

3.66 [2.90, 4.63]

Year 1987198819881990199119911991199119931993199419941994199519961997199920012005

Cocaine No cocaine Odds ratio Odds ratioM-H, Random, 95% CI

0.01 0.1 1 10 100CocaineNo Cocaine

LBW,low birthweight.


FIGURE 3Effect of antenatal cocaine exposure on PTB ( < 37 weeks)

Study or subgroupBingol 1987MacGregor 1987Chouteau 1988Cherukuri 1988Little 1989Neerhof 1989Fulroth 1989Hadeed 1989Gillogley 1990Calhoun 1991Kelley 1991Spence 1991Cohen 1991Bateman 1993Rosengren 1993

Kliegman, 1994Eyler 1994Shiono, 1995Miller 1995Kistin 1996Sprauve 1997Richardson 1999Ogunyemi 2004Bada 2005

Total (95% CI)Total eventsHeterogeneity: Tau² = 0.16; Chi² = 84.24, df = 23 ( P < .00001); I² = 73%Test for overall effect: Z = 10.92 ( P < .00001)

Events86

38281128

5133234

32035

1155

1181274719

1361480

457

1253

Total5024

1245553

1143556

13991286383

36121

20168175138

64483

62200

1068

3675

Events33

219

928

368

1622

43205457

4653

86860

1043540

2512

1671

4629

Total340

70218

55100

881021

56293

9130

348166387600

321168

7295276

130433158

302200

7559

36185

Weight3.6%1.4%4.8%3.4%1.6%3.6%2.9%3.1%4.6%1.7%1.2%4.8%4.6%6.4%2.8%

3.2%5.8%6.0%5.8%5.2%7.1%4.2%4.6%7.5%

100.0%

M-H, Random, 95% CI1.77 [0.77, 4.09]

11.33 [2.11, 60.96]4.63 [2.52, 8.48]

5.30 [2.18, 12.89]12.83 [2.73, 60.43]

3.26 [1.40, 7.56]4.56 [1.67, 12.44]

1.81 [0.69, 4.80]5.18 [2.73, 9.82]

26.54 [6.14, 114.79]1.68 [0.26, 10.89]

3.30 [1.78, 6.13]5.32 [2.81, 10.08]

2.88 [2.01, 4.14]2.98 [1.05, 8.43]

7.31 [2.87, 18.60]2.02 [1.30, 3.15]1.35 [0.89, 2.05]1.86 [1.18, 2.93]4.86 [2.83, 8.34]1.90 [1.53, 2.37]3.23 [1.57, 6.66]

10.44 [5.46, 19.98]2.64 [2.31, 3.01]

3.38 [2.72, 4.21]

Year 198719871988198819891989198919891990199119911991199119931993

199419941995199519961997199920042005

Cocaine No cocaine Odds ratio Odds ratio

M-H, Random, 95% CI

0.005 0.1 1 10 200No Cocaine Cocaine

PTB,preterm birth.






ate risk of bias and whether matched orunmatched controls were used for analyses. However, there was no statisticaldifference in the results between sub-groups ( P .05).

C OMMENT

A discussion about the effects of cocaine

use during pregnancy must be prefaced

with caution given the nature of theavailable evidence. Four issues are of particular concern: (1) the difculty of accurately measuring illicit substanceuse patterns among women throughoutpregnancy; (2) the difculty of separat-ing the effects of cocaine use from theeffects of the other confounding adverse

personal and social circumstances in

which substance use often takes place;(3) the common pattern of poly sub-stance use by this population; and (4)publication bias or the apparent review-er/editorial bias that results in preferen-tial publication in thescienticliteratureof studies that show unfavorable out-comes in association with substance

use.8

We explored the heterogeneity be-

FIGURE 4Effect of antenatal cocaine exposure on SGA ( < 10th percentile for GA)

Study or subgroupMacGregor 1987Cherukuri 1988Little 1989Hadeed 1989Neerhof 1989Kelley 1991Calhoun 1991Richardson 1991Miller 1995Kistin 1996Sprauve 1997Richardson 1999Ogunyemi 2004Bada 2005

Total (95% CI)Total eventsHeterogeneity: Tau² = 0.09; Chi² = 29.40, df = 13 ( P = .006); I² = 56%Test for overall effect: Z = 8.09 ( P < .00001)

Events6

111

1532

411

32319

1401819

297

599

Total24555356

114309134

13864

48362

2001071

2475

Events2303600

6132

1069410

260

1027

2639

Total7055

10056883091

600276

130433158

302200

7554

25623

Weight2.5%3.8%0.8%3.9%6.7%0.9%1.0%4.4%

11.7%12.5%19.9%

9.9%1.0%

21.3%

100.0%

M-H, Random, 95% CI11.33 [2.11, 60.96]

4.33 [1.14, 16.52]5.74 [0.23, 143.44]

6.46 [1.75, 23.83]5.33 [2.12, 13.44]

10.36 [0.53, 201.45]26.14 [1.52, 450.70]

0.86 [0.25, 2.88]1.52 [0.85, 2.72]4.73 [2.76, 8.11]2.74 [2.19, 3.42]4.34 [2.20, 8.57]

43.08 [2.58, 718.68]2.44 [2.10, 2.83]

3.23 [2.43, 4.30]

Year 19871988198919891989199119911991199519961997199920042005

Cocaine No cocaine Odds ratio Odds ratioM-H, Random, 95% CI

0.01 0.1 1 10 100No Cocaine Cocaine

GA, gestational age;SGA,small for gestational age.


FIGURE 5Effect of antenatal cocaine exposure on GA at delivery (weeks)

Study or subgroupMacGregor 1987Cherukuri 1988Little 1989Neerhof 1989Zuckerman 1989Cohen 1991

Kelley 1991Calhoun 1991Bateman 1993Singer 1994Eyler 1994Miller 1995Bandstra 2001

Total (95% CI)Heterogeneity: Tau² = 0.66; Chi² = 93.93, df = 12 (P < .00001); I² = 87%Test for overall effect: Z = 5.79 (P < .00001)

Mean36.637.438.937.538.836.9

37.93738

34.936.6

3739.4

SD4.2

31.43.72.33.3

2.93.72.74.1

54.21.4

Total245553

11411483

3091

361100168138253

1584

Mean39.339.239.3

3939.338.9

39.739.739.238.537.837.839.7

SD2

1.92.12.41.92.4

1.31.42.12.83.4

51.4

Total7055

10088

1010166

3091

387100168276147

2688

Weight4.5%7.3%8.7%7.6%9.1%7.8%

6.5%7.8%9.3%7.1%7.4%7.4%9.5%

100.0%

IV, Random, 95% CI-2.70 [-4.44, -0.96]-1.80 [-2.74, -0.86]-0.40 [-0.96, 0.16]

-1.50 [-2.34, -0.66]-0.50 [-0.94, -0.06]-2.00 [-2.80, -1.20]

-1.80 [-2.94, -0.66]-2.70 [-3.51, -1.89]-1.20 [-1.55, -0.85]-3.60 [-4.57, -2.63]-1.20 [-2.11, -0.29]-0.80 [-1.72, 0.12]

-0.30 [-0.58, -0.02]

-1.47 [-1.97, -0.98]

Year 198719881989198919891991

1991199119931994199419952001

Cocaine No cocaine Mean difference Mean differenceIV, Random, 95% CI

-4 -2 0 2 4Cocaine No cocaine

GA, gestational age.






tween studies by assessing clinical andstatistical heterogeneities and perform-ing subgroup analyses.

Another limitation includes the inac-

curacy in determining GA. Women whouse cocaine often lack prenatal care; pre-cise dating by last menstrual period orearly dating ultrasoundwere unavailable

forseveral studies. Some studies used theDubowitz score 9 to determine GA. Inac-curacies in dating can account for inac-curate reporting of PTB and SGA. How-

FIGURE 6Effect of antenatal cocaine exposure on BW (grams)

Study or subgroup

Bingol 1987MacGregor 1987Cherukuri 1988Hadeed 1989Little 1989Neerhof 1989Zuckerman 1989Cohen 1991Calhoun 1991Spence 1991Kelley 1991McCalla 1991Bateman 1993Forman 1993Eyler 1994

Singer 1994Miller 1995Bandstra 2001

Total (95% CI)

Heterogeneity: Tau² = 15296.60; Chi² = 58.96, df = 17 (P < .00001); I² = 71%Test for overall effect: Z = 13.63 (P < .00001)

Mean

2,4642,6772,5282,7952,9702,6442,8472,5562,6132,5202,6522,5602,7133,1622,704

2,6242,6262,971

SD

590706619448415685572642757

1,077540778569645742

769721474

Total

4224555653

11411483916330

12836137

168

100138253

1910

Mean

3,2323,3823,0563,3053,2953,2173,2543,2633,3403,1273,2683,1513,1743,3912,988

2,9892,9433,331

SD

475551500345433612617558494777487699573573721

750926514

Total

307705556

10088

101016691

34830

983387563168

100276147

4945

Weight

5.3%3.2%4.8%6.2%6.4%5.5%7.0%5.9%5.4%3.7%3.9%6.3%7.6%4.8%6.0%

4.8%5.9%7.2%

100.0%

IV, Random, 95% CI

-768.00 [-954.18, -581.82]-705.00 [-1015.55, -394.45]-528.00 [-738.29, -317.71]-510.00 [-658.10, -361.90]-325.00 [-465.30, -184.70]-573.00 [-752.34, -393.66]-407.00 [-518.68, -295.32]-707.00 [-869.12, -544.88]-727.00 [-912.72, -541.28]-607.00 [-885.19, -328.81]-616.00 [-876.21, -355.79]-591.00 [-732.69, -449.31]-461.00 [-542.88, -379.12]-229.00 [-442.15, -15.85]

-284.00 [-440.45, -127.55]

-365.00 [-575.54, -154.46]-317.00 [-479.50, -154.50]-360.00 [-461.57, -258.43]

-491.52 [-562.18, -420.85]

Year

198719871988198919891989198919911991199119911991199319931994

199419952001

No cocaine Cocaine Mean difference Mean differenceIV, Random, 95% CI

-1000 -500 0 500 1000Cocaine No cocaine

BW,birthweight.


TABLE 2Sensitivity/subgroup analysis

Variable Group

PTB LBW

n studies/participants OR (95% CI)

n studies/participants OR (95% CI)

Year of study 1991 13/3791 4.29 (3.11–5.92) 8/3032 5.23 (3.72–7.34)..........................................................................................................................................................................................................................................................................

1991 11/36069 2.93 (2.28–3.76) 11/35764 3.02 (2.32–3.93)................................................................................................................................................................................................................................................................................................................................................................................

Method of exposure assessment Self-report 11/32123 2.97 (2.25–3.93) 12/32160 3.21 (2.29–4.48)..........................................................................................................................................................................................................................................................................

Objective 13/7737 3.80 (2.59–5.57) 7/6636 4.62 (3.09–6.89)................................................................................................................................................................................................................................................................................................................................................................................

Type of cohort Retrospective 13/28711 3.69 (2.75–4.95) 12/14501 3.97 (3.05–5.17)..........................................................................................................................................................................................................................................................................

Prospective 11/11149 3.09 (2.13–4.48) 7/24295 3.28 (1.96–5.47)................................................................................................................................................................................................................................................................................................................................................................................

Quality assessment (risk of bias) Minimal/low 18/37341 2.99 (2.42–3.70) 15/37081 3.66 (2.85–4.70)..........................................................................................................................................................................................................................................................................

Moderate 6/2519 5.44 (2.73–10.85) 4/1715 3.71 (1.72–7.99)................................................................................................................................................................................................................................................................................................................................................................................

Type of controls Matched 10/2387 4.35 (2.59–7.30) 7/1481 4.72 (2.67–8.34)..........................................................................................................................................................................................................................................................................

Unmatched 14/37473 2.94 (2.34–3.69) 12/37315 3.37 (2.59–4.39)................................................................................................................................................................................................................................................................................................................................................................................CI , condence interval;LBW , low birthweight;OR , odds ratio;PTB , preterm birth.

Gouin. Cocaine use during pregnancyon low birthweight andpreterm birth. Am J Obstet Gynecol 2011.





ever, despite this limitation, BW andLBW reports are unaffected by GA andremain signicantly lowerin cocaine-us-ing mothers. Consistency in the resultsbetween studies and thestrength of asso-ciation between cocaine use and PTB

suggests that the possibility of false-pos-itive results is less likely.The concomitant use of tobacco was

one of the major confounding factors inthis metaanalysis. In 1997, Hulse et al10

conducted a metaanalysis using studiesthat had adjusted for tobacco exposureand suggested that, despite tobacco use,maternal cocaine use independently contributes to LBW,and that the effect isgreater with heavier use. In this meta-analysis, we have included several addi-

tional studies that have focused on neo-natal outcomes and have providedsubgroup analyses to strengthen theassociation.

There are other environmental factorsthat could not be taken into account inthese studies. The possible interaction of social factorswiththepathophysiologicef-fects of cocaine could lead to an overesti-mation of its impact. These factors aredif-cult to study, quantify, and control.Therefore, theauthorsrely on theavailable

cohort or case-controlledstudies.This review summarizes adverse neo-natal outcomes related to cocaine expo-sure during pregnancy. Several investi-gators have explored interventions tostop or reduce cocaine consumption inpregnancy to improve perinatal out-comes. Interventions are diverse, thespectrum including standard prenatalcare11 to residential rehabilitation pro-grams. 12 Overall, there appears to be atrend toward improvement of perinatal

outcomes with interventions focused onreducing maternal cocaine exposure.Racine et al13 published results indicat-ing an improvement in BW and decreasein LBW with 4 or more prenatal care vis-its. Comfort et al 14 compared inpatientresidential versus outpatient substanceabuse treatment program. The perinataloutcomes following both of these inter-ventions were similar. 14 Limited researchsuggests that interventions to decrease co-caine exposure during pregnancy may be

effective. However, future studies areneeded to compare the different types of

interventions and to determine the beststrategies tohelppregnantwomenwhoarecocaine dependent and to reduce or pre-vent cocaine addiction.

C ONCLUSIONS

Maternal prenatal cocaine consumptionis signicantly associated with PTB,LBW, and SGA births. Cocaine use dur-ing pregnancy is a preventable contri-butor to adverse perinatal outcomes.Therefore, it is important to provide in-terventions and support to pregnantwomen who are cocaine dependent. Fu-ture studies controlling for confoundersand impact of intervention are needed.

C ONTRIBUTORS

All authors participated in writing theoriginal grant application, and weremembers of the steering committee. P.S.wastheprincipal investigatorand ledtheKnowledge synthesis team. K.G. andK.M. were principal investigators on thisproject, and collected articles, assessedfor inclusion and quality, retrieved data,performed metaanalyses. K.G. wrote therst draft and K.M. and P.S. critically re-viewed and revised the manuscript. Jo-seph Beyene was the team statisticianand contributed to the planning and su-pervision of data analyses.

M EMBERS OF K NOWLEDGE

S YNTHESIS G ROUP ON

DETERMINANTS OF

LBW/ PRETERM BIRTHS

Prakesh Shah, Associate Professor, Uni-versity of Toronto, Toronto, Canada

Kellie E. Murphy , Associate Professor,University of Toronto, Canada

Sarah D. McDonald, Assistant Profes-sor, McMaster University, Hamilton,Canada

EileenHutton,Associate Professor, Mc-Master University, Hamilton, Canada

Arne Ohlsson, Professor Emeritus,University of Toronto, Canada

Vibhuti Shah, Associate Professor,University of Toronto, Toronto, Canada

Christine Newburn-Cook, AssociateProfessor&AssociateDeanResearch,Uni-versity of Alberta, Edmonton, Canada

Corine Frick, Adjunct Professor, Uni-versity of Calgary, Calgary, Canada

Fran Scott, Associate Professor, DallaUniversity of Toronto, Toronto, Canada

Victoria Allen, Associate Professor,Dalhousie University, Halifax, Canada

Joseph Beyene, Associate Professor,University of Toronto, Toronto,

Canadaf

ACKNOWLEDGMENTSWe would sincerely like to thank Ms ElizabethUleryk, Chief Librarian at the Hospital for SickChildren, Toronto, for her contribution in devel-oping the search strategies and running thesearch on a periodic basis.

REFERENCES1. Barker DJ. Adult consequences of fetalgrowth restriction. Clin Obstet Gynecol 2006;

49:270-83.2. Peters H, Theorell CJ. Fetal and neonatal ef-fects of maternal cocaine use. J ObstetGynecolNeonatal Nurs 1991;20:121-6.3. Addis A, Moretti ME, Ahmed Syed F, Einar-son TR, Koren G. Fetal effects of cocaine: anupdated meta-analysis. Reprod Toxicol 2001;15:341-69.4. Bingol N, Fuchs M, Diaz V, Stone RK, Gro-misch DS.Teratogenicityof cocaine in humans.J Pediatr 1987;110:93-6.5. StroupDF,Berlin JA,Morton SC,et al.Meta-analysis of observational studies in epidemiol-ogy: a proposal for reporting. Meta-analysisOf Observational Studies in Epidemiology(MOOSE) group. JAMA 2000;283:2008-12.6. Shah PS,Zao J. Induced termination of preg-nancy and low birthweight and preterm birth: asystematic review and meta-analyses. BJOG2009;116:1425-42.7. Higgins JP, Thompson SG. Quantifying het-erogeneity in a meta-analysis. Stat Med2002;21:1539-58.8. Holzman C, Paneth N. Maternal cocaine useduring pregnancy and perinatal outcomes. Epi-demiol Rev 1994;16:315-34.9. Dubowitz L. Assessment of gestational ageinnewborn: a practicalscoringsystem.ArchDisChild 1969;44:782.10. Hulse GK,English DR,MilneE, HolmanCD,Bower CI. Maternal cocaine use and low birthweight newborns: a meta-analysis. Addiction1997;92:1561-70.11. ChazotteC,Youchah J,Freda MC.Cocaineusing during pregnancy and low birth weight:the impact of prenatal care and drug treatment.Semin Perinatol 1995;19:293-300.12. Elk R, Mangus L, Rhoades H, Andres R,Grabowski J. Cessation of cocaine use duringpregnancy: effects of contingency manage-ment interventions on maintaining abstinenceand complyingwith prenatal care. Addict Behav1998;23:57-64.13. Racine A, Joyce T, Anderson R. The asso-ciation between prenatal care and birth weight





amongwomenexposed to cocaine inNewYorkCity. JAMA 1993;270:1581-6.14. Comfort M, Kaltenbach KA. Biopsychoso-cial characteristics and treatment outcomes of pregnant cocaine-dependent women in resi-dential and outpatient substance abuse treat-ment. J Psychoactive Drugs 1999;31:279-89.15.

MacGregorSN,Keith LG,Chasnoff IJ, et al.Cocaine use during pregnancy:adverse perina-tal outcome. Am J Obstet Gynecol 1987;157:686-90.16. Cherukuri R, Minkoff H, Feldman J, Parekh A, Glass L. A cohort study of alkaloidal cocaine(“crack”) in pregnancy. Obstet Gynecol 1988;72:147-51.17. Chouteau M, Namerow PB, Leppert P. Theeffectof cocaine abuse on birth weightand ges-tational age. Obstet Gynecol 1988;72:351-4.18. Fulroth R, Phillips B, Durand DJ. Perinataloutcome of infants exposed to cocaine and/ or heroin in utero. Am J Dis Child 1989;143:

905-10.19. Hadeed AJ, Siegel SR. Maternal cocaineuse during pregnancy: effect on the newborninfant. Pediatrics 1989;84:205-10.20. Little BB, Snell LM, Klein VR, Gilstrap LC3rd. Cocaine abuse during pregnancy: mater-nal and fetal implications. Obstet Gynecol1989;73:157-60.21. Neerhof MG, MacGregor SN, Retzky SS,Sullivan TP. Cocaine abuse during pregnancy:peripartum prevalence and perinatal outcome. Am J Obstet Gynecol 1989;161:633-8.22. Zuckerman B, Frank DA, Hingson R, et al.Effects of maternal marijuana and cocaine useon fetal growth. N Engl J Med 1989;320:762-8.23. Gillogley KM,Evans AT,HansenRL, Samu-els SJ, Batra KK. The perinatal impact of co-caine, amphetamine, and opiate use detectedby universal intrapartum screening. Am J Ob-stet Gynecol 1990;163:1535-42.

24. Calhoun BC, Watson PT. The cost of ma-ternal cocaine abuse: I, perinatal cost. ObstetGynecol 1991;78:731-4.25. Cohen HR, Green JR, Crombleholme WR.Peripartum cocaine use: estimating risk of ad-verse pregnancy outcome. Int J Gynaecol Ob-stet 1991;35:51-4.26. Kelley SJ, Walsh JH, Thompson K. Birthoutcomes, health problems, and neglect withprenatal exposure to cocaine. Pediatr Nurs1991;17:130-6.27. McCalla S,Minkoff HL,FeldmanJ, et al.Thebiologic and social consequences of perinatalcocaine use in an inner-city population: resultsof an anonymous cross-sectional study. Am JObstet Gynecol 1991;164:625-30.28. Richardson GA,Day NL.Maternal andneo-natal effects of moderate cocaine use duringpregnancy. Neurotoxicol Teratol 1991;13:455-60.29. Spence MR, Williams R, DiGregorio GJ,Kirby-McDonnell A, Polansky M. The relation-

ship between recent cocaine use and preg-nancy outcome. Obstet Gynecol 1991;78:326-9.30. Bateman DA,Ng SK,Hansen CA,HeagartyMC. The effects of intrauterine cocaine expo-sure in newborns. Am J Public Health 1993;83:190-3.31. Forman R, Klein J, Meta D, Barks J, Green-wald M, Koren G. Maternal and neonatal char-acteristics following exposure to cocaine in To-ronto. Reprod Toxicol 1993;7:619-22.32. Rosengren SS, Longobucco DB, BernsteinBA, et al. Meconium testing for cocaine metab-olite: prevalence, perceptions, and pitfalls.Am JObstet Gynecol 1993;168:1449-56.33. Eyler FD, Behnke M, Conlon M, Woods NS,FrentzenB. Prenatalcocaineuse:a comparisonof neonates matched on maternal risk factors.Neurotoxicol Teratol 1994;16:81-7.34. Kliegman RM, Madura D, Kiwi R, EisenbergI, YamashitaT. Relation of maternalcocaine use

to the risks of prematurity and low birth weight.J Pediatr 1994;124:751-6.35. Neuspiel DR, Markowitz M, Drucker E. In-trauterine cocaine, lead, and nicotine exposureand fetal growth. Am J Public Health 1994;84:1492-5.36. Singer L, Arendt R, Song LY, Warshawsky

E, Kliegman R. Direct and indirect interactionsof cocaine with childbirth outcomes. Arch Pedi-atr Adolesc Med 1994;148:959-64.37. Miller JM Jr, Boudreaux MC, Regan FA. Acase-control study of cocaine use in preg-nancy. Am J Obstet Gynecol 1995;172:180-5.38. ShionoPH,Klebanoff MA,Nugent RP,et al. The impactof cocaine andmarijuanauseon lowbirth weight and preterm birth: a multicenterstudy. Am J Obstet Gynecol 1995;172:19-27.39. Kistin N, Handler A, Davis F, Ferre C. Co-caine and cigarettes: a comparison of risks.Paediatr Perinat Epidemiol 1996;10:269-78.40. Sprauve ME, Lindsay MK, Herbert S,

Graves W. Adverse perinatal outcome in partu-rients who use crack cocaine. Obstet Gynecol1997;89:674-8.41. Richardson GA, Hamel SC, Goldschmidt L,DayNL. Growthof infants prenatally exposed tococaine/crack: comparison of a prenatal careand a no prenatal care sample. Pediatrics1999;104:e18.42. Bandstra ES, Morrow CE, Anthony JC, etal. Intrauterine growth of full-term infants: im-pact of prenatal cocaine exposure. Pediatrics2001;108:1309-19.43. OgunyemiD, Hernandez-LoeraGE. The im-pact of antenatalcocaine useon maternalchar-acteristics and neonatal outcomes. J MaternFetal Neonatal Med 2004;15:253-9.44. Bada HS, Das A, Bauer CR, et al. Low birthweight and preterm births: etiologic fraction at-tributable to prenatal drugexposure. J Perinatol2005;25:631-7.





APPENDIX 1Risk of bias assessment for observational studies

Bias None Low Moderate High Can’t tell

Selection ● Consecutive unselectedpopulation

● Sample selected fromgeneral populationrather than a selectgroup

● Rationale for case andcontrol selectionexplained

● Follow up orassessment timeexplained

● Sample selected from largepopulation but selectioncriteria not dened

● A select group ofpopulation (based on race,ethnicity, residence, etc)studied

● Sample selection ambiguousbut sample may berepresentative

● Eligibility criteria notexplained

● Rationale for case andcontrols not explained

● Follow up or assessmenttime not explained

● Sample selectionambiguous andsample likely notrepresentative

● A very selectpopulationstudied makingit difcult togeneralizendings

●

................................................................................................................................................................................................................................................................................................................................................................................

Exposureassessment

● Direct questioning(interview) orcompletion of surveyby mother regarding

her BW or GA

● Assessment of exposurefrom global dataset(National register, Vitalstatistics)

● Extrapolating data frompopulation exposure sample(with some assumptions)and not direct assessment

at any time

● Indirect methodof assessment(obtaining datafrom others and

not from motheror father)

●

................................................................................................................................................................................................................................................................................................................................................................................

Outcomeassessment

● Assessment fromhospital record, birthcerticate or fromdirect question tomother regarding BWof infant

● Assessment fromadministrative database(national register, vitalstatistics)

● Direct question to motherregarding gestational age

● Assessment from “open-ended’ questions (was yourinfant early? or premature?or small? or before duedate)

● Assessmentfromnonvalidatedsources orgeneric estimatefrom overallpopulation

●

................................................................................................................................................................................................................................................................................................................................................................................

Confoundingfactor

● Controlled for commonconfounders

● Only certain confoundersadjusted

● Not controlled forconfounders

................................................................................................................................................................................................................................................................................................................................................................................

Analytical ● Analyses appropriatefor the type of sample

●

Analytical methodaccounted for samplingstrategy in cross-sectional study

● Sample size calculationperformed andadequate samplestudied

● Analyses not accountingfor common statistical

adjustment (eg, multipleanalyses) when appropriate● Sample size calculation not

performed, but all availableeligible patients studied

● Sample size calculated andreasons for not meetingsample size given

● Sample size estimationunclear or only subsample

of eligible patients studied

● Analysesinappropriate for

the type ofsample/study

●

................................................................................................................................................................................................................................................................................................................................................................................

Attrition ● 0-10% attrition andreasons for loss offollow-up explained

● All subjects frominitiation of study to thenal outcome

assessment wereaccounted for

● 0-10% attrition andreasons for loss of follow-up not explained

● 11-20% attrition, reasonsfor loss of follow-upexplained

● 11-20% attrition butreasons for loss of follow-upnot explained

● 20% attrition but reasonsfor loss of follow-upexplained

● All subjects from initiation ofstudy to nal outcomeassessment not accountedfor

● 20% attrition,reasons for lossof follow-up notexplained

●

................................................................................................................................................................................................................................................................................................................................................................................BW , birthweight;GA,gestational age.






APPENDIX 2Studies quality assessment (risk of bias) of included studies of cocaine exposure

Author Type of studySelectionbias

Exposureassessment bias

Outcomeassessmentbias

Confoundingfactor bias

Analyticalbias

Attritionbias

Overallassessmentbias

Bingol et al4 Prospective cohort with unmatched controls Low None None Low Low Low Low................................................................................................................................................................................................................................................................................................................................................................................

MacGregor et al15 Cohort with matched controls Low None None Low Low None Low................................................................................................................................................................................................................................................................................................................................................................................

Cherukuri et al16 Retrospective cohort with matched controls Low None None Moderate Low None Low................................................................................................................................................................................................................................................................................................................................................................................

Chouteau et al17 Retrospective cohort with unmatchedcontrols

Low None None Moderate Low None Low

................................................................................................................................................................................................................................................................................................................................................................................

Fulroth et al18 Cohort with unmatched controls Moderate None None Moderate Low None Moderate................................................................................................................................................................................................................................................................................................................................................................................

Hadeed, Siegel19 Retrospective cohort with matched controls Low Low None Low Low None Low................................................................................................................................................................................................................................................................................................................................................................................

Little et al20 Retrospective cohort with unmatchedcontrols

Low None None Low Low None Low

................................................................................................................................................................................................................................................................................................................................................................................

Neerhof et al21 Prospective cohort with unmatched controls Moderate None None Moderate Low None Moderate................................................................................................................................................................................................................................................................................................................................................................................

Zuckerman et al22 Prospective cohort with unmatched controls Low Low None Low Low Low Low................................................................................................................................................................................................................................................................................................................................................................................

Gillogley et al23 Retrospective cohort with matched controls Low None None Low Low Moderate Low................................................................................................................................................................................................................................................................................................................................................................................

Calhoun, Watson24 Prospective cohort with matched controls Moderate Low None Low Low None Moderate................................................................................................................................................................................................................................................................................................................................................................................

Cohen et al25 Retrospective cohort with matched controls Low None None Low Low None Minimal................................................................................................................................................................................................................................................................................................................................................................................

Kelley et al26 Retrospective cohort with matched controls Low None None Moderate Low ns Moderate................................................................................................................................................................................................................................................................................................................................................................................

McCalla et al27 Cross-sectional cohort with unmatchedcontrols

Low None None Low Low Moderate Low

................................................................................................................................................................................................................................................................................................................................................................................

Richardson andDay28

Prospective cohort with unmatched controls Low None None Low Low Moderate Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Spence et al29 Prospective cohort with unmatched controls L ow None None Moderate Low Low Low................................................................................................................................................................................................................................................................................................................................................................................

Bateman et al30 Prospective cohort with unmatched controls Low None None None Low ns Low................................................................................................................................................................................................................................................................................................................................................................................

Forman et al31 Prospective cohort with unmatched controls Low None None Low Low None Low................................................................................................................................................................................................................................................................................................................................................................................

Rosengren et al32 Prospective cohort with unmatched controls Low None None Moderate Low None Moderate................................................................................................................................................................................................................................................................................................................................................................................

Eyler et al33

Retrospective cohort with matched controls Low Low None None Low ns Low................................................................................................................................................................................................................................................................................................................................................................................

Kliegman et al34 Cohort with unmatched controls Low None None None Low ns Low................................................................................................................................................................................................................................................................................................................................................................................

Neuspiel et al35 Retrospective cohort with unmatchedcontrols

Low None None Low Low Moderate Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Singer et al36 Retrospective cohort with matched controls Low None none Low Low ns Low................................................................................................................................................................................................................................................................................................................................................................................

Miller et al37 Retrospective cohort with matched controls None None None None Low Low Minimal................................................................................................................................................................................................................................................................................................................................................................................

Shiono et al38 Prospective cohort with unmatched controls Low None None Low Low Low Low................................................................................................................................................................................................................................................................................................................................................................................

Kistin et al39 Retrospective cohort with unmatchedcontrols

Low None None Low Low None Low

................................................................................................................................................................................................................................................................................................................................................................................

Sprauve et al40 Retrospective cohort with unmatchedcontrols

Low None None None Low Low Low

................................................................................................................................................................................................................................................................................................................................................................................

Richardson et al41 Prospective cohort with unmatched controls Low None None Low Low Low Low................................................................................................................................................................................................................................................................................................................................................................................Bandstra et al42 Retrospective and prospective cohort with

unmatched controlsLow Low None None Low Moderate Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Ogunyemi,Hernandez-Loera43

Retrospective cohort with matched controls Moderate Low None Low Low Low Moderate

................................................................................................................................................................................................................................................................................................................................................................................

Bada et al44 Retrospective cohort with unmatchedcontrols

Low None None None Low Low Low

................................................................................................................................................................................................................................................................................................................................................................................



cocaína e gestação revisão 2010

Documents

Transcript of cocaína e gestação revisão 2010