9 Complications of Term

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  Complications of Term Pregnancies Beyond 37Weeks of Gestation  Aaron B. Caughey,  MPP ,  MPH , and Thomas J. Musci,  MD OBJECTIVE:  To estimate when rates of pregnancy complica-tions increase beyond 37 weeks of gestation. METHODS:  We designed a retrospective, cohort study of all women delivered beyond 37 weeks of gestational age from1992 to 2002 at a single community hospital. Rates of perinatal complications by gestational age were analyzed with both bivariate and multivariable analyses. Statisticalsignificance was designated by  P  < .05. RESULTS:  Among the 45,673 women who delivered at 37completed weeks and beyond, the rates of meconium andmacrosomia increased beyond 38 weeks of gestation ( P  < .001), the rates of operative vaginal delivery, chorioamnio-nitis, and endomyometritis all increased beyond 40 weeksof gestation ( P  < .001), and rates of intrauterine fetal deathand cesarean delivery increased beyond 41 weeks of gesta-tion ( P  < .001). CONCLUSION:  Risks to both mother and infant increase aspregnancy progresses beyond 40 weeks of gestation.(Obstet Gynecol 2004;103:57–62. © 2004 by The Ameri-can College of Obstetricians and Gynecologists.) LEVEL OF EVIDENCE: II-3 Itwasnotedin1951thatalthoughpregnanciespersisting  beyond 300 days occurred less than 5% of the time, theyaccounted for 30% of perinatal deaths. 1  Thus, since itsadvent,oneintentofantenatalfetalsurveillancehasbeenthe prevention of fetal death among postterm pregnan-cies. In the 1970s and 1980s, this was commonly definedas patients beyond 42 completed weeks, or 294 days, 2 which complicates more than 10% of pregnancies, 3 andthisremainsthedefinitionusedbytheAmericanCollegeof Obstetricians and Gynecologists (ACOG) today.However,theuseofa42-weekthresholdwasquestioned by Bochner et al 4 in a 1988 study, which showed adecreased rate of stillborn fetuses and fetal distress dur-ing labor in a group of patients who began antenataltesting at 41 weeks, as compared with the control group,which began testing at 42 weeks of gestational age. Thishasledtotestingstrategiesthatbeginincreasinglyearlierforpostdatestesting.Mostrecently,thegestationalageatwhich clinical concern should be raised was questionedin a study 5 that asserted that concerns regarding themorbidity and mortality of pregnancies at and beyondterm should be weighed against the risks of induction of labor. Traditionally, there has been concern that induc-tion of labor will lead to an increased rate of cesareandelivery. However, there are an increasing number of studies 5,6 that suggest this concern might be outweighed byrisksofotherpregnancycomplications.Furthermore,the concern regarding the increased rate of cesareandelivery related to induction might be unfounded whenconsidering research that finds that cesarean rates aresimilar between patients managed with induction versusexpectant management. 6,7 Given these changes over the past decades, the ques-tion remains: At what gestational age does the benefit of induction of labor outweigh that of expectant manage-ment? In addition to an increased perinatal mortalityrate, 4,5,8–10 numerous studies have associated postterm pregnancieswithincreasedratesofmeconiumandmeco-nium aspiration syndrome, 4,11 oligohydramnios, 12 mac-rosomia, 4,13,14 fetal birth injury, 15 fetal distress in la- bor, 4,10,16 and cesarean delivery. 4,14 Most studies 15,17,18 thatexaminegestationalagedosobyestablishingthresh-olds, such as 41 or 42 weeks, and comparing rates of complications beyond this threshold with those in pa-tients delivered below the threshold. However, stud-ies 5,19,20 that have examined the risk of fetal death byweek of gestational age show that rates increase in asteadily rising fashion before 42 weeks of gestation. If thiscomplicationofpregnancyincreasesnotasadiscreterisk beyond some particular gestational age, but insteadcontinuously with increasing gestational age, other com- plicationsassociatedwithposttermpregnanciesmightdothe same.  From the Department of Obstetrics, Gynecology and Reproductive Sciences, Uni- versity of California, San Francisco; and Department of Obstetrics and Gynecology,California Pacific Medical Center, San Francisco, California.Dr. Caughey is supported by the National Institute of Child Health and Human Development, Grant #HD01262 as a Women’s Reproductive Health Research Scholar. VOL. 103, NO. 1, JANUARY 2004 57 © 2004 by The American College of Obstetricians and Gynecologists. 0029-7844/04/$30.00Published by Lippincott Williams & Wilkins. doi:10.1097/01.AOG.0000109216.24211.D4   Another theoretic concern with the existing literatureregarding perinatal complications of pregnancy is thequality of the pregnancy dating. Because we have im- proved the dating of pregnancy with the use of ultra-sound, we are now better able to identify pregnanciesthat go beyond 280 days of gestation. 21,22 Bennett et alrecently showed that up to 10% of pregnancies will beredated by a second-trimester ultrasound and more than20%byafirst-trimesterscan(BennettK,CraneJ,O’SheaP, Lacelle J, Hutchens D, Copel J. Combined first andsecond trimester ultrasound screening is effective in re-ducing postterm labor induction rates: A randomizedcontrolled trial [abstract]. Am J Obstet Gynecol 2002;187:S68). Therefore, studies that examined complica-tions of pregnancy in populations whose pregnancieswere dated primarily by history and physical examina-tion alone are likely to suffer from nondifferential mis-classification of gestational age.In this setting of improved pregnancy dating and adesire to find trends by week of gestation rather thansimple dichotomous comparisons, we sought to explorecomplications of pregnancy beyond 37 weeks among anotherwise low-risk group of patients. Specifically, wewere interested in estimating at what gestational age therates of maternal and fetal complications increase overthe prior week of gestation. Further, we were interestedin whether these complications continued to increase beyond the initial rise and in what fashion. MATERIALS AND METHODS  We designed a retrospective, cohort study of all womendelivered beyond 37 weeks of gestational age from Jan-uary 1, 1992, to July 31, 2002, at California PacificMedicalCenterinSanFrancisco.CaliforniaPacificMed-ical Center is a community hospital that performs morethan 40% of all deliveries in San Francisco and, otherthan high-risk transfer patients, nearly all patients whodeliver at California Pacific Medical Center receive pre-natal care from a California Pacific Medical Center–affiliated provider. Institutional review board approvalwas obtained from the Committee on Human Researchat California Pacific Medical Center. Patients were in-cluded in the analysis if they delivered a singleton preg-nancybeyond37weeksofgestation.Gestationalagewasdetermined in relation to the estimated date of confine-ment, as defined by 280 days from the last menstrual period that was either less than 7 days different from afirst-trimester ultrasound or 14 days different from asecond-trimester ultrasound. Otherwise, the estimateddates of confinement from the earliest ultrasound wereused. The following variables were also exported fromtheCaliforniaPacificMedicalCenterperinataldatabase:maternalage,ethnicity,professionandeducation,lengthof labor, mode of delivery, parity, prior mode of deliv-ery, anesthesia, birth weight, amniotic fluid characteris-tics, and labor management. The outcome variablesintrauterine fetal death, Apgar scores, admission to theintensive care nursery, chorioamnionitis, and endomyo-metritiswerealsoincluded.Characterizationofamnioticfluid, endomyometritis, and chorioamnionitis werecoded by the attending physicians into the clinical data- base. Macrosomia was defined as birth weight greaterthan or equal to 4500 g. After variables were abstractedfrom the database, all patient identifiers were removed before analysis. This study was approved by the inves-tigational review board at California Pacific MedicalCenter. The data were then compiled and analyzed withSTATA 7 software (Stata Corp., College Station, TX).Because the primary predictor of interest was gestationalage by week, the dependent variables of interest werecompared in a bivariate fashion with gestational agefrom 37 weeks and beyond. For those variables of inter-est, as well as those that exhibited an increasing bivari-ate trend before 42 weeks of gestation, a multivariablelogistic regression was performed, including possibleconfounders, and with dummy variables for each weekof gestation in the model as independent variables.Cross-product terms to examine interaction between predictor variables were created. Their contribution tothe model was tested with the maximum likelihood ratiotest, and they were only kept in the model if they werestatistically significant; this was designated by a  P   valueless than .05. RESULTS During the study period, there were 45,673 women whodelivered beyond 37 completed weeks of gestation. These patients were predominantly well-educated, as Table 1.  Demographics and Descriptive Obstetric OutcomesVariable  n   (%) Maternal age  35 y 15,281 (33.4)College graduate 26,247 (57.3)EthnicityBlack 1493 (3.3) Asian 17,786 (38.8)Hispanic 1658 (3.6) White 22,753 (49.7)Other (Asian Indian, mixed race) 1983 (4.3)Nulliparous 24,501 (53.5)Birth weight  4000 g 4667 (10.2)Cesarean delivery 8417 (18.4)Operative vaginal delivery 7510 (16.4) 58 Caughey and Musci  Complications of Term Pregnancy  OBSTETRICS & GYNECOLOGY  indicated by the 57% who had completed 4 years of college (Table 1). When complications of pregnancywere examined by gestational age, there was a clearincrease in the rates of meconium and macrosomia asearly as 38 weeks of gestation (Table 2). In addition tothe rates of meconium and macrosomia, intensive carenursery admissions, Apgar scores less than or equal to 6,operative vaginal delivery, chorioamnionitis, and en-domyometritis all increased beyond 40 weeks of gesta-tion (Tables 2 and 3). All of the perinatal outcomes thatincreased beyond 40 weeks continued to increase be-yond 41 weeks of gestation. At this point, the rates of intrauterine fetal death and cesarean delivery also beganto increase and continued to rise beyond 42 weeks of gestation as well.Gestational age was examined with multivariable lo-gistic regression, controlling for maternal age, ethnicity,and education, mode of delivery, birth weight, length of labor, and induction as appropriate in the different mod-els. Beyond 40 weeks, it was found to predict an in-creased risk for moderate or thick meconium, intensivecare nursery admission, macrosomia, 5-minute Apgarscore less than or equal to 6, chorioamnionitis, andoperative vaginal delivery (Table 4) when comparedwith pregnancies delivered before 40 weeks of gestation. These risks were further increased beyond 41 weeks of gestation, and intrauterine fetal death, endomyometritis,and primary cesarean delivery were also found to beincreased among these pregnancies. Interestingly, therisk for intrauterine fetal death was more than 2.5 timesgreater between 41 and 42 weeks of gestation as com- pared with before 40 weeks of gestation. In this samecomparison, rates of macrosomia and moderate or thickmeconium were tripled and doubled, respectively.Cross-product terms were not found to be significant inany of the models and were not used in the final models. DISCUSSION  We found that there were a number of complications of  pregnancy that rose between 39 and 41 weeks of gesta-tion; that is, before the current threshold of 42 weeks of gestation, which is used to define postterm pregnancy. These complications were all examined in multivariablemodels, and gestational age beyond 40 and 41 weekswere predictive of increased risk even when controlling for known confounders. Most concerning among thesewere the rates of intrauterine fetal death and intensivecare nursery admissions. The fact that intensive carenursery admissions increase is concerning both for neo- Table 2.  Fetal Complication Rates by Week of GestationGestationalage wk ( n  ) Meconium (%)Intrauterine fetal death *(per 10,000) Macrosomia(per 1000)Intensive care nurseryadmissions (%) 37 (3964) 3 2.4 1.0 7.438 (8865) 5 † 3.6 5.3 † 4.5 † 39 (13,839) 8 † 4.0 9.5 † 3.940 (12,456) 13 † 2.6 14.6 † 5.0 † 41 (5685) 17 † 9.2 † 30.4 † 5.4  42 (864) 18 34.7 † 60.2 † 7.2 ‡ Statistically significant results are as compared with the rate of complication in the prior week of gestation.* Therateofintrauterinefetaldeathisreportedperallwomenpregnantataparticulargestation,theat-riskpopulationforintrauterinefetaldeath. All other complications are reported per deliveries at a particular gestation. † P   .001 (   2 test). ‡ P   .05 (   2 test). Table 3.  Maternal Complication Rates by Week of GestationGestational%age wk ( n  )Operative vaginaldelivery (%)Primary cesareandelivery (%)Chorioamnionitis(%)Endomyometritis(per 1000) 37 (3964) 14.1 14.2 1.2 8.638 (8865) 14.4 15.1 1.5 6.4*39 (13,839) 15.5 † 14.0 1.7 7.7 ‡ 40 (12,456) 17.9* 15.9* 2.3* 9.6*41 (5685) 18.5 21.2* 2.7 15.3*  42 (864) 17.4 25.0 † 3.6 † 22.0 ‡ Statistically significant results are as compared with the rate of complication in the prior week of gestation.*  P   .001 (   2 test). † P   .05 (   2 test). ‡ P   .01 (   2 test). 59 VOL. 103, NO. 1, JANUARY 2004  Caughey and Musci  Complications of Term Pregnancy  natal morbidity and mortality, but also for the use of medical resources and costs. Further research will needto investigate long-term neonatal outcomes to seewhether these concerns are well founded. We also found increases in the rates of meconium andmacrosomia beyond 38 weeks in the bivariate compari-son and 40 weeks in the multivariable analysis. Thesefindings are markers for other neonatal morbidity andmortality associated with meconium aspiration syn-drome 23 and birth injury. 24  We did not examine therates of these more severe outcomes, and even in ourdatasetwithmorethan45,000patients,itisquestionablewhether we would have enough power to investigatesuch findings. Thus, in our analysis, meconium andmacrosomia served as risk factors for these more seriousneonatal complications.Pregnancies that are more accurately dated are morelikely to exhibit complications of pregnancy sooner in populationstudies.Ifoneweretoexaminecomplicationsof pregnancy in a cohort of patients who were misdated,thefindingswouldbebiasedtowardriskincreasesoccur-ring later in pregnancy. This is described by epidemiol-ogists as  nondifferential misclassification  , and is based on thefollowing. Assume that half of the pregnancies are mis-dated under and half are misdated over the actual gesta-tional age. Thus, the patients who are misdated earlierthan they truly are (ie, their due date is set later thanwhat it should be, so they are always perceived as being earlier than their actual gestational age) will have theircomplications recorded as occurring earlier in gestationthan actually happened. This will lead to an increase inthe overall number of complications in earlier weeks of gestation. The patients who are misdated later than theytruly are will actually be at earlier gestational ages thanstated, which will decrease the overall number of com- plicationsoccurringinlaterweeksofgestation.Thus,thedifference between later and earlier weeks of gestationwill be narrowed by nondifferential misdating. The improved dating of pregnancies might reveal anumber of findings in perinatal epidemiology previouslyhidden by this nondifferential misclassification that oc-curs by the use of just the history and physical examina-tion for dating, as compared with ultrasound. As pa-tients’ pregnancies are better dated, it is important toelucidate the risks in these pregnancies in a rigorousfashion. Knowing these risks will improve clinicians’ability to counsel their patients and enable researchers toexplore a variety of predictors and explanations. Finally, both clinicians and researchers will be able to investigatethe use of interventions to decrease these risks. Cur-rently,antenatalfetalsurveillanceisusedtohelpidentifythoseposttermpatientsatanevenhigherriskofperinatalcomplications. With further evidence consistent withwhat we have found in this study, it might be reasonableto consider such screening at an earlier gestational age.If antenatal testing is begun at an earlier gestationalage, it is reasonable to assume that more patients withneed for delivery will be identified. The efficacy and risk profile of the existing and new methods for labor induc-tion will continue to change over time. Thus, we willneedtoreassesstherisksandthebenefitsfromexpectantmanagement versus labor induction in these patientswith only the most current data. If labor inductionmethods improve and the risks of increasing gestationalage begin earlier than previously suspected, there might beanindicationtointerveneatanearliergestationalage.Given our data, it might be found that the balance of risks and benefits for intervention in low-risk pregnan-cies should be earlier than current management. Themost recent recommendations by ACOG have definedthat threshold to be at 42 weeks of gestation. However, Table 4.  Association of Gestational Age With Perinatal Complications in Multivariable Model * Outcome40 wk GA 41 wk GA 42 wk GAOR (95% CI) OR (95% CI) OR (95% CI) Intrauterine fetal death 0.93 (0.77, 1.11) 2.69 (1.08, 7.29) 4.16 (1.16, 14.78)Moderate or thick meconium 1.74 (1.61, 1.89) 2.19 (1.99, 2.41) 2.28 (1.89, 2.75)Intensive care nursery admissions 1.12 (1.01, 1.24) 1.12 (1.02, 1.26) 1.53 (1.12, 1.93)Macrosomia 1.63 (1.29, 2.04) 3.43 (2.72, 4.33) 7.04 (5.06, 9.08)5-min Apgar score  6 1.61 (1.20, 2.16) 2.00 (1.44, 2.78) 2.23 (1.24, 4.00)Chorioamnionitis 1.21 (1.07, 1.36) 1.21 (1.04, 1.41) 1.66 (1.24, 2.22)Endomyometritis 1.08 (0.88, 1.33) 1.46 (1.14, 1.87) 1.76 (1.09, 2.84)Operative vaginal delivery 1.11 (1.04, 1.23) 1.14 (1.05, 1.23) 1.07 (0.88, 1.23)Primary cesarean delivery 1.13 (1.03, 1.27) 1.32 (1.17, 1.53) 1.46 (1.12, 1.89) GA  gestational age; OR  odds ratio; CI  confidence interval.* Eachoutcomewasexaminedinaseparatemultivariableanalysisandcomparedwithpregnanciesdeliveredat39weeksofgestation,controlling for maternal demographics, length of labor (except intrauterine and fetal death cesarean delivery), induction (except intrauterine fetal death), and birth weight (except macrosomia). 60 Caughey and Musci  Complications of Term Pregnancy  OBSTETRICS & GYNECOLOGY
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