ry

Ba

tetr

European Journal of Obstetrics & Gynecology and Reproductive Biology 173 (2014) 2933

e t

Contents lists available at ScienceDirect

European Journal of ObsteReproductiv

jou r nal h o mep ag e: w ww .e l1. Introduction

Maternal mortality is the death of women while pregnant orwithin 42 days of termination of pregnancy, irrespective of theduration and the site of pregnancy, from any cause related to oraggravated by the pregnancy or its management, but not fromaccidental or incidental causes [1]. Delayed maternal mortality isdened as maternal death after the 42nd postnatal day but withinthe rst postnatal year.

In order to further rene this measure from the point of view ofmedical statistics, the maternal mortality ratio (MMR) has beenintroduced dened as the number of maternal deaths per 100,000live births. Maternal mortality is classied by etiology as eitherdirectly attributable to obstetric conditions or attributable toother medical conditions not directly associated with obstetric

complications. Maternal mortality due to other medical conditionsmay either result from a medical condition present beforegestation exacerbated by the physiological processes occurringduring pregnancy or it may develop de novo during the gestationperiod [24].

The Millennium Development Goals (MDG) program wasestablished to nd concrete solutions regarding ve speciccommunity health issues, three of which relate to improvingmaternal and perinatal fetal health [5,6]. The program highlightedthe urgency of reducing the MMR within countries with lessdeveloped infrastructure. This recognition of urgency gave birth tothe Countdown to 2015 Initiative [5], which focuses exclusively oncommunity health issues directly related to maternal and fetalhealth.

It was recognized that in order to protect the health of thepregnant mother and to reduce maternal mortality, a medicaldatabase of obstetric data is necessary with precise parameterscapable of being statistically evaluated. In 2005 the World HealthOrganization (WHO), United Nations Childrens Fund (UNICEF),United Nations Population Fund (UNFPA) and the World Bank

Received 9 April 2013

Received in revised form 23 October 2013

Accepted 1 November 2013

Keywords:

Maternal mortality

Obstetric causes of maternal death

Indirect causes of maternal death

Thromboembolic complications of

pregnancy

Hungarian results with those of other European countries.

Study design: Cases of maternal death in Hungary during the study period from calendar year 1978 to

2010 were analyzed in a retrospective manner to characterize mortality distribution and to identify

potential clinical or demographic predictors. Data in all cases were extracted both from the national

Obstetric Registry operated by the National Institute of Gynecology and Obstetrics, from the Hungarian

Central Bureau of Statistics and from the National Public Health and Medical Ofcer Service. Detailed

clinical data were obtained based on obligatory reporting by individual clinical institutions.

Results: The annual maternal mortality rate (MMR) was 26.7 per 100,000 live births in the period 1978

1987 and declined signicantly to 10.9 per 100,000 live births in the period 19972010. In the period

19881996 (with missing associated clinical and demographic data) the MMR was 16.4 per 100,000 live

births. The proportion of delivery-associated causes of death increased signicantly between the two

study periods from 49.4% to 62.9% (p < 0.05). Among obstetric causes of death, the rate of

thromboembolism showed a signicant increase, while there was a trend toward a decline in rate of

maternal deaths attributable to hemorrhagic shock. Among medical causes of death not directly

attributable to obstetric complications, the rate of renal and gastrointestinal etiologies declined

signicantly throughout the study periods.

Conclusions: We observed a marked decline in maternal mortality during the last few decades in

Hungary. Recent changes in mortality distribution highlight current characteristics of pregnancy care in

Hungary and may help identify strategies for future improvement.

2013 Elsevier Ireland Ltd. All rights reserved.

* Corresponding author at: Semmelweis University 1st Department of OB/GYN,

Barossutca 27, 1088 Budapest, Hungary. Tel.: +36 1 459 15 00; fax: +36 1 317 61 74.

E-mail address: joogabor@hotmail.com (J.G. Joo).

0301-2115/$ see front matter 2013 Elsevier Ireland Ltd. All rights reserved.http://dx.doi.org/10.1016/j.ejogrb.2013.11.004Trends in maternal mortality in Hunga

Janos Rigo Jr.a, Gyorgy Csakany b, Marcella Laky a, Jozsef Gabor Joo a,*a Semmelweis University, Faculty of Medicine, First Department of Gynecology and ObsbDepartment of Gynecology and Obstetrics, Del-Pesti Hospital, Budapest, Hungary

A R T I C L E I N F O

Article history:

A B S T R A C T

Objective: We evaluated th between 1978 and 2010

lint Nagy a, Endre Horvath a,

ics, Budapest, Hungary

rends of the last decades in maternal mortality in Hungary and compared

trics & Gynecology ande Biology

sev ier . co m / loc ate /e jo g rb

J. Rigo Jr. et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 173 (2014) 293330established global parameters in order to standardize datareporting relating to maternal and perinatal fetal mortality incountries where these parameters remain unacceptably high [7,8].At the same time, in more developed European countries theEURO-PERISTAT data processing system handles all obstetricstatistical parameters including the ones related to maternalmortality [9].

The rst Hungarian obstetric registry was founded in 1931 byVilmos Tauffer, the medical director of the Second Department ofGynecology and Obstetrics in Budapest. As the rst such dataregistry in the world, the Hungarian Obstetric Registry includeddata relating to several obstetric complications and describedtrends in maternal mortality [10]. In this study we analyzed trendsin maternal mortality in the last few decades in Hungary. We alsocompared Hungarian results with those of other Europeancountries.

2. Materials and methods

During the study period of 19782010, we analyzed theHungarian obstetric registry data in a retrospective manner toevaluate trends in maternal mortality and of associated clinical anddemographic parameters. There was a gap in data reportingbetween 1988 and 1996. In these years very signicant politicalchanges happened in Hungary, which have had also seriousconsequences on changes of the health policy of our country.Probably a suitable data reporting system of maternal death caseswas not available in these years, and that may be the reason for thelack of adequate information from this period, when only the totalnumber of maternal deaths was reported, with relevant clinicaland demographic data missing. Due to this gap, our descriptivedata are dichotomous, consisting of two separate periods, i.e. onebefore (19781988) and one after (19972010) the gap. Data in allcases were extracted both from the national Obstetric Registryoperated by the National Institute of Gynecology and Obstetrics,from the Hungarian Central Bureau of Statistics and from theNational Public Health and Medical Ofcer Service [11]. Detailedclinical data were obtained based on obligatory reporting byindividual clinical institutions.

The following clinical parameters were included in our analysis:maternal age, parity, neonatal birth weight, cause of death andtime of death. Time of death was dened as gestational age at deathif the mother expired during pregnancy (in weeks), or time afterdelivery (in weeks) if maternal death occurred in the postnatalperiod.

Cause of maternal deaths was identied based on clinicaldiagnosis reported through diagnostic coding as per the 10thInternational Classication of Diseases (ICD10) system [1,12].Cause of death was dened as a clinical condition occurring duringgestation or during the rst 42 days postnatally either associatedwith an obstetric complication or attributable to a pre-existingmedical problem exacerbated during pregnancy. In the determi-nation of cause of death, no consideration of length of gestation orlocalization of pregnancy (ectopic pregnancy) was made. Adverseevents arising during an obstetric procedure or failure ofperforming an obstetric procedure in a timely manner wereregarded as valid causes of maternal death [7,13]. Proceduresassociated with trauma cases were not included in this category.

Classication of causes of maternal mortality according to theICD10 coding system was based on whether that death was theresult of an obstetric complication or other medical condition [4,8].The denitions are as follows. Direct obstetric cause: death of themother results from obstetric complications of the pregnant state(pregnancy, labor, and puerperium), from interventions, omis-sions, incorrect treatment, or from a chain of events resulting fromany of the above [1]. Indirect obstetric cause: maternal deathresults from previous existing disease or diseases that developedduring pregnancy and which was not due to direct obstetric causes,but which was aggravated by the physiologic effects of pregnancy[1].

In the group of direct obstetric causes, the obstetric conditionshemorrhagic shock, sepsis, preeclampsia, thromboembolism anddeath associated with general anesthesia were included. Deathsattributable to a pre-existing medical condition or a medicalcondition arising during pregnancy but not directly attributable toan obstetric cause were subsequently classied by organ systemsin which the specic condition resulting in death was thought tooriginate as cardiovascular, neurological, pulmonary, gastrointes-tinal, renal, tumor-associated and miscellaneous organ system.Deaths associated with trauma and deaths from an unknown causewere classied as a separate category from either obstetric ormedical causes and labeled as miscellaneous cause of death.

In situations where the cause of death could be attributed tomultiple obstetric or medical conditions, the case was reviewed bya panel of clinicians to determine the primary cause of death, but incertain cases we had to take into consideration two or more causesof death due to the lack of a clinical basis to make a preferenceamong them.

Cases of maternal mortality were divided into three groupsbased on maternal age: group 1 37 years. In cases wherematernal death occurred during pregnancy, three gestational agecategories were created: 37 weeks.

SPSS statistical software was used for analysis of the data.Parameters of descriptive statistics and other clinical variableswere categorized by calendar year. Only those cases were includedin a given analytical procedure in which all relevant data could beextracted for the procedure.

Our study protocol was approved by the local research ethicscommittee at Semmelweis University (approval number: TUKEB433492/2013/EKU(519/2013)).

3. Results

In the study period 19781987, a total of 358 maternal deathsoccurred compared to only 151 in the study period 19972010; inboth of these periods associated clinical and demographic datawere available for evaluation. In the study period 19881996,however, the 167 deaths that were reported could not be analyzeddue missing clinical and demographic data.

In the period 19781987, the median age of maternal mortalitycases was 30.7 years with a range of 1946 years. In the studyperiod 19972010, the median age was 32.7 years with a range of2044 years. In the group of maternal mortality cases where deathoccurred during pregnancy, the median gestational age was 31.8weeks with a range of 2841 weeks in the former study period,whereas in the latter the median gestational age was 31.6 weekswith a range of 2540 weeks. There was no signicant differencebetween median values in the two study periods. In contrast, asignicant difference in parity between the two study periods wasfound, with the period 197887 having a higher parity (2.62)compared to the study period 19972010 (2.23; p < 0.05). Nosignicant difference was found in neonatal birthweight betweenthe two study periods (2675 416 g vs. 2594 353). A signicantreduction in MMR from 26.7/100000 live births in 197887 to 10.9/100000 live births 19972010 study period (p < 0.05) was observed(Table 1). In the period 19881996, i.e. the period with missingassociated clinical and demographic data, MMR was 16.4/100000 livebirths (MMR19781987 vs. MMR19881996; p < 0.05; MMR19881996 vs.MMR19972010; p > 0.05).

There was no signicant difference in maternal age distributionbetween the two study periods (19781987:

3136 years 35%; 37 years 21.2%; 19972010: 0.05). There was not a single

Table 1Clinical characteristics of maternal mortality cases in the study period 19781987 versus 19972010.

Clinical characteristics 19781987 (n = 358) 19972010 (n = 151) p

Median maternal age (years) (mean; minimummaximum) 30.7 (range 1946) 32.8 (range 2044) NS

Median gestational age at delivery (weeks) (mean; minimummaximum) 31.8 (range 2841) 31.6 (range 2540) NS

Parity (mean SD) 2.62 2.0 2.23 2.1

rio

J. Rigo Jr. et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 173 (2014) 293332case of death associated with general anesthesia in the secondstudy period (Table 4).

Between the study periods there was a non-signicant rise inthe rate of non-obstetric cardiovascular deaths from 30.9% to 47.2%(p > 0.05), while their absolute number decreased from 43/139 to25/53 cases. There was also a non-signicant rise in the rate of non-obstetric tumor-related deaths from 10.1% to 17.0% (p > 0.05), anda decrease in absolute number from 14/139 to 9/53. A signicantdecline from 10.1% to 1.9% (p < 0.05) was noted in the rate of renalmortality between the study periods, while the absolute numberdecreased from 14/139 to 1/53 cases. A similar signicant decreasefrom 10.8% to 1.9% (p < 0.05) was detected in the rate ofgastrointestinal mortality between the study periods, withabsolute numbers decreasing from 15/139 to 1/53 cases (Table 5).

4. Comments

During the study period, the median age of maternal mortalitycases in Hungary was similar to that found in other Europeancountries [1420]. In spite of continuous improvements inobstetric medical care in Hungary over the last three decades, itis clear that increased maternal age, a common trend throughoutEurope, increases the risk of certain obstetric complications.Among others, these risks include delivery-related maternal death,maternal death due to thromboembolic complications and deathdue to cardiovascular diseases in pregnancy. Clearly advanced

Fig. 1. Changes in maternal mortality ratio (MMR) during the pematernal age requires a different approach in obstetric care,compared to care regimens required for younger obstetric patients.

In both study periods the median gestational age was close to32 weeks, suggesting that the third trimester poses the greatestrisk for maternal mortality. A French study reported that in theirpopulation two-thirds of maternal mortality cases occurred afterthe 37th gestational week, suggesting that this risk furtherincreases toward the end of pregnancy [13]. Management of thethird trimester requires close follow-up of patients, with a focus onprevention and early recognition of complications which may leadto maternal mortality.

It is important to note that most maternal deaths attributable toa complication after an obstetric event (delivery or miscarriage)occurred within the rst 24 h and least commonly after the 30thday. This time dynamic suggests that close monitoring duringhospitalization is especially important within the rst 24 h afterdelivery.

A global report by the WHO in 2008 provides international dataregarding recent trends in maternal mortality in multiple countries[11]. In this report, countries are divided into three categories (A, B,C) based on the reliability of their registry data; Hungary belongs tocategory A, signaling a high degree of reliability in terms of registrydata.

The MMR in Hungary between 1997 and 2010 proved to be 10.9per 100,000 live births. The last Europeristat Report (2010) states adifferent value (13.4 per 100,000 live births) for the period 20062010. The discrepancy between the values may be due to thediffering lengths of the study periods [21], but also the lower MMRin 20032004 (7.4 per 100,000 live births) may stand in thebackground of this phenomenon [22]. Among neighboringcountries, the MMR was found to be lower in Austria and Slovakia,while in Romania and the Ukraine, results were higher than thosereported in Hungary (Fig. 1) [23]. Regarding the time dynamics ofMMR decline, a signicant decline similar to the one reported inthe present study was seen in the last twenty years both in EasternEuropean countries formerly belonging to the communist bloc andin European countries with high gross domestic product (GDP)such as Sweden or Germany [13,23].

During the study period, a notable decline of deaths associatedwith either abortion or ectopic pregnancy was seen, while theproportion of deaths attributable to delivery-related complicationsrose. In terms of abortion, the more widespread use of the vacuumaspiration technique and quality improvement in anesthesiaprocedures likely played a role. We suggest that the decreaseddeath rate associated with ectopic pregnancy may be a result ofimproved diagnostic procedures and consequent prompt surgical

d 19902010 in countries used as reference in our study [19].interventions.While in the study period of 19781987 hemorrhagic shock was

the most common cause of death, followed by sepsis andthromboembolism, deaths attributable to hemorrhagic shockdeclined (without signicance) by the study period 19972010and these three most important causes of death becameapproximately equally common. Historical reports from Austriaand from Switzerland revealed that in these countries hemorrhagicshock remained the most common obstetric complication leadingto maternal deaths, followed by thromboembolism and pre-eclampsia [19,24].

In their recent study published earlier this year, Rossi andMullin reported that in their study population of 9750 cases fromdifferent European countries, hemorrhagic shock and preeclamp-sia were the most common causes of death, with a relative percentdistribution of around 22% each [23].

Another study described the distribution of causes of maternaldeaths in several countries in the period 20032004 [25]. Althoughthe short span of this study does not allow far-reachingconclusions, it is noteworthy that in economically developed

countries hemorrhagic shock, thromboembolism and preeclamp-sia contributed nearly equally to maternal deaths.

In our investigations the only obstetric cause of death whichshowed a signicant difference between the study periods wasthromboembolism, with a rate increasing from 19.4% to 29.8%. Dueto this increase, genetic testing for predisposition for thromboem-bolic complications among patients having a positive personal orfamily history is an important task of the obstetrician, as it may aidin the prevention of this life-threatening complication.

Concerning medical causes of death not directly associated withobstetric complications, we report a relatively high frequency ofcardiovascular deaths in our population, followed by centralnervous system and tumor-related deaths. Our data conform to

Conict of interest

The authors declare no conict of interest.

References

[1] World Health Organization. International statistical classication of diseasesand related health problems. 10th Revision. 2nd ed. Geneva: WHO; 2004.

[2] Gulmezoglu AM, Pattinson RC, Hofmeyr GJ, Lumbiganon P. Global maternaland perinatal health issues. In: James DK, Steer PJ, Weiner CP, Gonik B, editors.High risk pregnancy management options. 4th ed., USA: Elsevier, St. Louis;2011. p. 17.

[3] MacKay AP, Berg CJ, Duran C, et al. An assessment of pregnancy-relatedmortality in the United States. Paediatr Perinat Epidemiol 2005;19:20614.

[4] Khan KS, Wojdyla D, Say L, et al. WHO analysis of causes of maternal death: asystematic review. Lancet 2006;367:106674.

J. Rigo Jr. et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 173 (2014) 2933 33similar reports from Austria, in contrast to Dutch results showing anearly equal incidence of cardiovascular and central nervoussystem-related deaths [15,20]. Regarding the statistical value ofthe changes of rates of medical causes of death between the twostudy periods, only the decline of the incidence of renal (10.1% vs.1.9%) and gastrointestinal diseases (10.8% vs. 1.9%) are worthmentioning.

A different approach is necessary to reduce maternal mortalityassociated with obstetric complications. To improve survival, earlydiagnosis of obstetric conditions known to increase risk formaternal mortality appears necessary, together with continuousquality improvement in pregnancy care.

Our study has several potential limitations. One limitation mayhave been the potential failure of reporting delayed maternalmortality cases to the registry. This could be caused by the failureof medical professionals to report such cases, especially undercircumstances when maternal death was not associated with anobstetric condition. Another study limitation may have beenrelated to a potential pitfall known to occur in assigning theappropriate cause of death to maternal mortality cases. This arisesfrom the difculty in determining whether death occurred due toan obstetric condition or as a result of a specic complicationassociated with that condition.

Due to international experience with under-reporting maternalmortality, an international system has developed where dataprovided by national registries are adjusted by the estimateddegree of underreporting for that particular country [13,26]. Withregard to the Hungarian national registry, an adjustment factor of1.5 has been established which reects a relatively favorablereliability of Hungarian data reporting.

In summary, our study suggests that maternal mortality inHungary has signicantly declined in the last several decades.Among causes of death, delivery-associated complications haveincreased in importance while deaths associated with eitherabortion or ectopic pregnancy declined. Among deaths directlyattributable to obstetric complications, a signicant decline inhemorrhagic shock cases was identied. On the other hand, a trendtoward rising rates of thromboembolic complications was observed.[5] www.countdown2015mnch.org.[6] United Nations General Assembly. United Nations Millennium Declaration. A/

RES/55/2. New York: United Nations; 2000.[7] Alexander S, Wildman K, Zhang W, et al. Maternal health outcomes in Europe.

Eur J Obstet Gynecol Reprod Biol 2003;111(Suppl. (1)):S7887.[8] Wildman K, Bouvier-Colle MH, MOMS Group. Maternal mortality as an indi-

cator of obstetric care in Europe. BJOG 2004;111:1649.[9] www.europeristat.com/images/doc/EPHR/european-perinatal-health-report.

pdf.[10] Lampe L, Batar I, Szallasi A. Semmelweis Egyetem Altalanos Orvostudomanyi

Kar. II. Szamu Szuleszeti es Nogyogyaszati Klinika. In: Lampe L, Batar I, SzallasiAau, editors. The history of the Hungarian Obstetrics and Gynecology. Buda-pest: Medicina Kiado; 2009. p. 6982.

[11] www.ksh.hu.[12] WHO, UNICEF, UNFPA. The World Bank. Trends in maternal mortality: 1990

2010; 2013, www.unfpa.org.[13] Bouvier-Colle MH, Mohangoo AD, Gissler M, et al. What about the mothers? An

analysis of maternal mortality and morbidity in perinatal health surveillancesystems in Europe. BJOG 2012;119:8809.

[14] Saucedo M, Deneux-Tharaux C, Bouvier-Colle MH. Understanding regionaldifferences in maternal mortality: a national casecontrol study in France.BJOG 2012;119:57381.

[15] Schutte JM, de Jonge L, Schuitemaker NW, et al. Indirect maternal mortalityincreases in the Netherlands. Acta Obstet Gynecol Scand 2010;89:7628.

[16] Vrachnis N, Iliodromiti S, Samoli E, et al. Maternal mortality in Greece, 19962006. Int J Gynaecol Obstet 2011;115:169.

[17] Donati S, Senatore S, Ronconi A. Regional maternal mortality working group.Maternal mortality in Italy: a record-linkage study. BJOG 2011;118:8729.

[18] Bdker B, Hvidman L, Weber T, et al. Maternal deaths in Denmark 20022006.Acta Obstet Gynecol Scand 2009;88:55662.

[19] Bollini P, Wanner P, Pampallona S. Trends in maternal mortality in Switzerlandamong Swiss and foreign nationals, 19692006. Int J Public Health2011;56:51521.

[20] Karimian-Teherani D, Haidinger G, Waldhoer T, et al. Under-reporting of directand indirect obstetrical deaths in Austria, 198098. Acta Obstet Gynecol Scand2002;81:3237.

[21] www.tno.nl/downloads/european_perinatal_health_report_2010.pdf.[22] www.europeristat.com/reports/european-perinatal-health2004.html.[23] Rossi C, Mullin P. The etiology of maternal mortality in developed countries: a

systematic review of literature. Arch Gynecol Obstet 2012;285:1499503.[24] Fassler M, Zimmermann R, Quack Lotscher KC. Maternal mortality in

Switzerland 19952004. Swiss Med Wkly 2010;140:2530.[25] Deneux-Tharaux C, Berg C, Bouvier-Colle MH, et al. Underreporting of preg-

nancy-related mortality in the United States and Europe. Obstet Gynecol2005;106:68492.

[26] Kao S, Chen LM, Shi L, Weinrich MC. Underreporting and misclassication ofmaternal mortality in Taiwan. Acta Obstet Gynecol Scand 1997;76:62936.