A Nationwide Survey of Risk Factors for Stillbirth in Taiwan, 2001—2004
Objective:The purpose of this study was to evaluate the nationwide stillbirth rate and explorethe potential risk factors associated with stillbirths.
Patients and methods:Data from vital registrations during the time period from January 1,2001 through to December 31, 2004 in Taiwan were used. Stillbirth was defined as fetal deathwith more than 20 completed weeks’ gestational age (GA) or with birth weight more than 500 gif the GA was not known.
Results:There were a total of 8481 stillbirths identified nationwide between January 1, 2001and December 31, 2004. The stillbirth rate was nine per 1000 total births in the study period,and the proportionate decline was nearly 48.8% in the most recent decade. There was a significant increase in average maternal age during this period. Advanced maternal age and teenagepregnancy were independent significant risk factors for stillbirths even after accounting for theeffects of medical conditions that were more likely to occur among these particular agegroups. Those fetuses that had been exposed to cord prolapse, maternal cervical incompetence and oligohydramnios/polyhydramnios were especially vulnerable. By contrast, women who had foreign nationality, fetal ultrasound surveys, fetal heart beat monitoring andhastened parturition were less likely to have stillbirth.
Conclusion:The stillbirth rate in Taiwan has remained high despite advancements in medicalcare. Prenatal evaluation of high risk women may decrease the adverse fetal outcomes.
Copyright©2012, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rightsreserved.
1. Introduction
Stillbirth, the death of a fetus late in pregnancy before theonset of labor, accounts for two thirds of perinatal deaths.1For international comparisons, the World Health Organization (WHO) has defined stillbirth as fetal loss beyond20 weeks of gestation, or if gestational age (GA) is unknownwith birth body weight ≥500 g.1,2It is estimated thatworldwide, 3.2 million babies are stillborn annually; the trueincidence is probably higher because of the limitations ofavailable data and the fact that stillbirths are underreported. Up to 99% of these stillbirths occur in developingcountries, with half (51%) occurring in India, China, Pakistan,and Bangladesh.3Despite higher numbers of stillbirthsreported in southeast Asian countries, data on this topic fromthis area have been scarce. The rate of stillbirth has beenthought to be declining during recent decades in Taiwan.However, the nationwide fetal death data had not beenroutinely recorded in Taiwan up to the present time. Theestimated stillbirth rate in case control studies was reportedto be 57/1000 total births during the mid 1960s to 1970s andaround 17.6/1000 total births from 1991 to 1996,respectively.4e6Preventing stillbirths is of great importancein improving global child health, which is the fourth goal inthe Millennium Development Goals proposed by the UnitedNations.7Understanding the risk factors for stillbirth willhelp obstetricians design effective interventions for thefetus. Early identification of those women who are at risk ofstillbirth will help the provision of targeted antepartumtesting regimens to improve outcomes.
The National Health Insurance that has operated since1995 in Taiwan has greatly enhanced the accessibility ofprenatal caring programs to pregnant women and comprehensive prenatal care to motherefetus dyads. The objective of this study was to examine the nationwide stillbirthrate and explore the potential risk factors for stillbirths inTaiwan.
2. Patients and Methods
Stillbirth was defined as stated above. GA determinationwas mainly based on the last menstrual period or ultrasound examination. The nationwide stillbirth rate wasestimated from the data of birth and stillbirth certificatesobtained from vital registration in Taiwan. The vital registration statistics have been documented by the Ministry ofthe Interior since 1978 and have been annually reported bythe Bureau of Health Promotion since 1998. We studied thepopulations that included all stillbirths and live birthsduring the time period from January 1, 2001 to December 31, 2004. This study was approved by the InstitutionalReview Board of National Taiwan University College ofPublic Health.
The maternal characteristics and the obstetrical andprenatal antecedents between live births and stillbirthswere compared. Studentttest, Pearson’sc2test, andFisher’s exact test were used appropriately to distinguishthe characteristic differences between study groups.Logistic regression analysis was used, and odds ratios (ORs)were calculated with 95% confidence intervals (CIs) usinga low-risk reference group before and after adjustment formaternal sociodemographic characteristics to evaluate theeffect of each maternal and fetal clinical characteristic onthe risk of stillbirth. The population attributable risk (PAR)was calculated for each significant risk factor OR estimateand the prevalence of stillbirth cases by using the followingequation:
PARZproportion of cases exposed to the factor×1000×(OR-1)/OR.8,9All tests of hypothesis were twotailed, with a type 1 error rate fixed at 5%. All calculations were performed using SPSS version 12 (SPSS Inc.,Chicago, IL, USA) for Windows.
3. Results
There were a total of 8481 stillbirths and 932,497 live birthsbetween January 1, 2001 and December 31, 2004 in Taiwan.The stillbirth rate was 9.01 per 1000 births. There wasa significant increase in the advanced maternal age duringthe study period in Taiwan (Table 1). Both mothers olderthan 40 years (ORZ2.98; 95% CI 2.67, 3.32) and pregnantteenagers (ORZ2.57; 95% CI 2.29, 2.89) had a significantlyincreased risk of stillbirth compared with mothers aged25 years to 29 years. Maternal age was significantly associated with adverse fetal outcome even after taking into account the effects of maternal medical conditions(Table 2).
Multiple gestations have markedly increased the risk ofadverse fetal outcome. The adjusted risk of stillbirth wasincreased by three and six times for twins and triplets,respectively, compared with singleton births. There were52.3% males and 47.6% females born during the study period.Fetal sex had no significant association with stillbirth. NonTaiwanese mothers including women from southeast Asiancountries and mainland China accounted for 12.6% of ourstudy population. Foreign women (ORZ0.67; 95% CI 0.62,0.73) conferred an independent lower risk for stillbirth thanTaiwanese women after adjustment of maternal sociodemographic and medical characteristics (Table 2).
Mothers with a previous history of preterm/low-birthweight delivery or delivery of a giant baby had a higher riskof stillbirth for the current pregnancy. With regard tomaternal medical diseases, pregnant women with cervicalincompetence, oligohydramnios or polyhydramnios, Rhblood type incompatibility, or chronic hypertension orhypertensive disorders of pregnancy had adjusted odds ofstillbirth several times greater than those of womenwithout these conditions before or during pregnancy. Theseassociations remained unchanged after an additionaladjustment for maternal age, ethnicity, parity, fetal sex,and GA (Table 3).
The presence of obstetrical complications greatlyincreased the risk of stillbirth including umbilical cordprolapse (ORZ12.7; 95% CI 9.38, 17.2), abruption ofplacenta, maternal fever, and premature rupture ofmembrane (latency>12 hours). In addition, antepartum or peripartum hemorrhage (ORZ1.85; 95% CI 1.48, 2.31),meconium stain of amniotic fluid, placenta previa, andbreech/malpresentation were associated with stillbirth(Table 4).
The PAR of the most common identifiable maternalfactors of stillbirths were oligohydramnios and/or polyhydramnios (29%), followed by cervical incompetence(16%), anemia (10%), and previous birth of a preterm or lowbirth weight infant (8%) (Table 3). For stillbirths groupedaccording to prenatal characteristics, the largest proportion of fetal deaths was ascribed to premature rupture ofmembrane (49%), followed by abruption of placenta (22%),breech and/or malpresentation of the fetus (15%), andmaternal fever>38C (14%) (Table 4).
On the other hand, pregnancy with cephalopelvicdisproportionate, poor labor progression, and prolongedlabor was each associated with a decreased risk of stillbirth, with an odds ratio of 0.06, 0.17, and 0.21, respectively (Table 4). Also, there were protective effectsobserved for those women who had undergone fetal heartbeat monitoring by cardiotocography (ORZ0.48; 95% CI0.44, 0.52), hastened parturition (ORZ0.62; 95% CI 0.56,0.69), and prenatal fetal ultrasound examinations(ORZ0.93; 95% CI 0.87, 0.99) after adjustment forpotential confounding factors (Table 5). Prenatal interventions such as induction, chorionic villus sampling,tocolysis, cervical cerclage, and amniocentesis were allfound to be associated with increased risk of stillbirth.
The incidences of congenital anomalies among stillbirthand live birth groups were 24.4% and 0.7%, respectively,with a significant difference between groups (Table 6).
4. Discussion
During the past decade, stillbirths have declined by nearly50% to 9.01 per 1000 births in Taiwan. Advances in obstetrical practice may contribute to the reduction in stillbirthrate to some degree by preventing specific causes of fetaldeath. However, epidemiological studies concerning stillbirth in Taiwan are scarce. This current nationwide surveywith the calculation of PAR for each potential risk factor ofstillbirth might provide a more reliable estimate of thisimportant public health problem.
Our finding was consistent with the data of previousstudies that advanced maternal age was an important riskfactor for stillbirth.10e13This study showed that the risk ofstillbirths of fetuses among mothers over 40 year of age washighest and gradually decreased to reach a lowest point
among mothers of 25-29 years old. The risk increased againwith younger maternal ages. Such findings remainedunchanged after adjustment for potential confoundersincluding maternal medical and sociodemographic characteristics. We found that the risk of stillbirth began to rise atyounger ages (30e35 years) compared to those previouslyreported (≥35 years of age).6The reason underlying theprogressed stillbirth hazard in the younger population wasunclear. Stressful life styles, biophysical redox reactionsdue to hazardous environmental exposures, and improvedhealth care for chronic illnesses in this particular age groupwere some of our concerns that require further investigation. Despite the marked reduction in the rate of stillbirthscompared with the data in the 1960s and 1970s in Taiwan,there was an upward trend in incidence of stillbirths from8.5 to 9.9/1000 total births from 2001 through 2004. Theincrease might be due to the improving national stillbirthand neonatal birth registration system in Taiwan that hasbeen under regular surveillance and validation by theBureau of Health Promotion since 1998. Likewise, there wasalso a trend of increased stillbirth reported in the UK due toimproved data collection system.14In addition, the incidence of stillbirth usually increases in rapidly industrializing areas where women tend to delay childbearing. Moreeffort should be made on balancing industrial developmentand the wellbeing of future generations.
This study revealed that the progressively increasingproportions of immigrant mothers from southeast Asiancountries and China had potential impacts on obstetricoutcomes. The disparities of stillbirth hazard had beenobserved between different race/ethnicities.15The situation in Taiwan was different from that of most western
countries. Despite lower parental education, advancingpaternal age, and spatial distribution disparity, babies bornto married immigrant mothers in Taiwan had favorableneonatal outcomes. The non-Taiwanese foreigners hada significantly lower stillbirth rate compared to Taiwanesemothers after controlling potential confounders. Thirteenpercent of newborns are born to immigrant mothersnowadays, and the rate continues to grow. The healthymother effect may have an influence on the lower incidence of stillbirth among immigrant mothers.16,17Theimpacts on health issues may be shown in the overall longterm outcomes in the future, and continuing observation iswarranted.
The relationship between fetal sex and pregnancyoutcomes remains unclear.18We did not observe a signifi-cant difference of risk for stillbirth between male andfemale fetuses. However, fetuses with unrecognizablegender occurred in the stillbirth group, therefore, the oddsratio cannot be accurately calculated in this report.
Preterm delivery and small for GA had been reported asrisk factors for subsequent stillbirth.19We found thatwomen with previous preterm labor and low-birth-weightinfant delivery had increased stillbirth risk, with PARaround 7.9%. This was higher than that of a previousreport.20We also observed a positive correlation betweenhistory of delivering large infant and stillbirth in latergestation. The exact mechanism of how the previouspregnancy outcome influences intrauterine survival of thefollowing pregnancy is not well understood. One possibilityis that similar maternal conditions influence both gestations. Detailed pregnancy history should be providedregarding the potential risk of subsequent pregnancy.
Cervical incompetence during pregnancy was signifi-cantly associated with the risk of stillbirth. Cervical cerclage therapy for women with short cervical length hadcontroversial results with regard to fetal loss reduction indifferent randomized control trials.21This study showedthat under the guidance for treatment of at-risk women,there was still increased risk of stillbirths. Further study isneeded to investigate effective management of cervicalincompetence.
Abnormality in the volume of amniotic fluid, either oligohydramnios or polyhydramnios, was a major risk of stillbirth, with an OR of 13.9 and PAR of 29.1%. Amniotic fluid is primarily composed of fetal urine and lung fluid thatcirculates between the fetal body compartments, theplacenta, and the amniotic cavity, and is swallowed by thefetus in late trimester. Several studies found that abnormality in the volume of amniotic fluid in prenatal surveillance was associated with increased risk of deceleration infetal heart beat, increased incidence of cesarean deliveryfor fetal distress, and lower Apgar scores.21e25However,the precise correlation between the volume of amnioticfluid and the incidence of stillbirth has been hard to estimate. The appropriate management of otherwise nonproblematic pregnancy with abnormality in the volume ofamniotic fluid also remains uncertain.24,26Thoroughexamination and aggressive management of pregnancieswith oligohydramnios or polyhydramnios may help decreasethe risk of adverse fetal outcome.
In addition to the abovementioned prenatal factors,adverse fetal outcomes among surveyed obstetricalcomplications in this study also included: cord prolapse,abruptio placenta, maternal fever, premature rupture ofmembrane (PROM) over 12 hours, intrapartum hemorrhage,meconium stain of liquor, placenta previa, and breech/malposition of fetus. PROM with a latent period of morethan 12 hours emerged as the single best predictor forstillbirth. PROM places a fetus at great risks of intrauterineinfection and probable cord compression due to decreasedamniotic fluid volume. The result of this report should rousethe special attention of clinical practitioners regarding thisparticularly high-risk population in order to prevent adversepregnancy outcomes. Treatment with amnioinfusion forpatients with PROM did not show enough evidence forreducing caesarean section rate, incidence of low Apgarscores, or neonatal death.26Optimal management of PROMdepends on careful evaluation of clinical situation for eachcase by experienced obstetricians.
Maternal medical diseases, despite comprehensiveprenatal care, increased the risks of stillbirth, similar toprevious reports.27e29The higher incidence of stillbirthobserved among pregnant women who had receivedamniocentesis, chorionic villus sampling, induction forlabor, tocolysis, or cervical cerclage may be to some extenta reflection of the underlying maternal and fetal medication conditions. However, we also found decreased risks ofstillbirth among women with cephalopelvic disproportionate, poor labor progression, and prolonged labor in thispopulation-based study that were different from previousreports.30e32Our results may be attributed to the improvedperinatal health care system in modern society. We speculated the risk of stillbirth in pregnancy with cephalopelvicdisproportionate, poor labor progression, and prolongedlabor may be decreased after further perinatal management including choice of Cesarean section as soon as theseconditions were diagnosed. The value of OR became insignificant after the consideration of exclusion of cesareansection (data not shown).
We found that aggressive fetal monitoring by ultrasonography and cardiotocography had marked protectiveeffects of reducing stillbirth. The public health implicationsof these findings are substantial. Taiwan has a grossdomestic product (GDP) per capita of more than US $16,000beyond the year 2006, and its public health care system hasimproved greatly during the recent decade. The deaths of
most stillbirth babies may be avoidable, as evidenced bythe low stillbirth rate of four per 1000 total births seen inindustrialized countries relative to stillbirth rates of 40 orhigher per 1000 total births seen in countries with thepoorest health care systems. We also found that hastenedparturition was less likely to result in stillbirth. Laboraugmentation is usually accomplished by artificial ruptureof membrane or oxytocin injection when active laborbecomes irregular and infrequent or the cervix stopsdilating. Decreased stillbirth risk among women whounderwent labor augmentation to hasten the deliveryprocesses may result from improved perinatal care orintensive fetal monitoring. Further reduction of stillbirthrate in high-income countries through applications ofsurveillance and introduction of information to pregnantwomen to increase maternal awareness of abnormal fetalactivity was reported in one cohort study.28The improvement of general prenatal health care accessibility duringthe past decade in Taiwan may have marked impacts onpregnancy outcomes. This study provided further clues foridentification of high-risk pregnancies and potentiallyeffective screening methods together with various promising interventions for these women.
There remain limitations to our study. The possibility ofresidual confounding by unmeasured concomitant riskfactors or illnesses might be associated with maternal andgestational outcomes, such as maternal nutritional status,interpregnancy interval, or environmental tobacco exposure. The variations of PAR for risk factors of stillbirthbetween our study and previous studies may be due todifferent prevalence of exposures in different populationsettings and to accuracy in the estimation of the stillbirthrate. The nationwide certification data for stillbirthsurveillance in our study may possess the best estimationand lower the chance of inaccuracy.
We did not have information on detailed conditions andseverity of abnormal amount of amniotic fluid and could notdifferentiate the effects of oligohydramnios from those ofpolyhydramnios. Despite these limitations, this nationwidepopulation-based study may minimize the biases andprovide robust epidemiological evidence for advocatingbetter perinatal care.
In conclusion, this study demonstrated that the majorrisk factors associated with stillbirths in Taiwan includeyoung and advanced maternal age, maternal history ofhematological disorders, oligohydramnios, polyhydramnios,antepartum hemorrhage, and umbilical cord prolapse. Earlyidentification and appropriate perinatal management ofthese factors are important issues in the promotion ofmaternal and child health.
Acknowledgments
This study was supported in part by grants from the Bureauof Health Promotion, Department of Health (DOH94-HP-1802 and DOH95-HP-1802) of Taiwan.