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Article ID: WMC004510 ISSN 2046-1690

Live births resulting from advanced abdominalextrauterine pregnancy, a review of cases reportedfrom 2008 to 2013Peer review status:No

Corresponding Author:Dr. Gwinyai Masukume,-, Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University ofthe Witwatersrand - South Africa

Submitting Author:Dr. Gwinyai Masukume,-, Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University ofthe Witwatersrand - South Africa

Previous Article Reference: http://www.webmedcentral.com/article_view/4477

Article ID: WMC004510

Article Type: Research articles

Submitted on:13-Jan-2014, 06:50:42 PM GMT Published on: 14-Jan-2014, 02:51:19 AM GMT

Article URL: http://www.webmedcentral.com/article_view/4510

Subject Categories:OBSTETRICS AND GYNAECOLOGY

Keywords:Abdominal pregnancy, Extrauterine pregnancy, Live birth, Placenta, Sex ratio at birth

How to cite the article:Masukume G. Live births resulting from advanced abdominal extrauterine pregnancy, areview of cases reported from 2008 to 2013. WebmedCentral OBSTETRICS AND GYNAECOLOGY2014;5(1):WMC004510

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Live births resulting from advanced abdominalextrauterine pregnancy, a review of cases reportedfrom 2008 to 2013Author(s): Masukume G

Abstract

Introduction:Advanced abdominal pregnancy isclassically defined as a pregnancy that hasprogressed beyond 20 weeks of gestation in which thefetus is growing and developing in the mother’sabdominal cavity. Advanced abdominal pregnancies,in particular those with live births can provide a uniqueand useful opportunity to understand certainreproductive biologic phenomena.

Methods: PubMed, Scopus and Google Scholar weresearched for English language articles that reported alive birth resulting from an advanced abdominalpregnancy from 2008 (the year of the last major reviewon advanced abdominal pregnancy) to 2013.

Results: 38 cases of an advanced abdominalpregnancy resulting in a live birth were identified from16 countries. 37.5% males at births (normal average51.5% males at birth) were observed in this study.

Conclusion: Physiologically males are morevulnerable than females from conception; thepresumed hostile extrauterine environment ofadvanced abdominal pregnancy may cause excessdemise of males compared to females.

Introduction

Advanced abdominal pregnancy (AAP) is classicallydefined as a pregnancy that has progressed beyond20 weeks of gestation in which the fetus is growingand developing in the mother’s abdominal cavity, orthe fetus shows signs of having been in the mother’sabdominal cavity [1].

Ovarian, broad ligament and tubal pregnancies areexcluded from AAPs definition; however this omissionhas been contested because from a clinicalperspective these pregnancies pose similar diagnosticand therapeutic challenges as AAPs [2]. Others are ofthe opinion that a placenta implanted in the peritonealcavity is the best way to define an AAP [3].Furthermore, the greater than 20 weeks of gestationcutoff is arbitrary.

An AAP resulting in a live birth is extremely rare. Thisis because abdominal pregnancy has an incidence ofabout 1 in 400 to 50 000 deliveries [4]; the variableincidence depends on the characteristics of aparticular geographic region. In addition, because thefetus is outside the uterus, AAP has a high maternaland perinatal morbidity and mortality. It is estimatedthat a woman with an abdominal pregnancy is 90times more likely to die in comparison to a woman withan intrauterine pregnancy [5]. On average, more thanhalf of AAP babies die [1]. About 20% of AAP infantshave malformations or deformations [6].

AAP can be primary or secondary (see Illustration 1).Primary AAP where there is direct implantation of theconceptus into the abdominal cavity is the lesscommon type; certain criteria have to be met for anAAP to be classified as being primary [7]. SecondaryAAP due to fimbrial abortion, tubal rupture, ruptureduterus or a ruptured uterine rudimentary horn is themore common type.

An over distended uterus (with excessive stretching ofthe myometrium) for example occurring with twins wasin the 1980s considered to be involved in the etiologyof pre-eclampsia [8]. Cases of pre-eclampsia occurringwith AAP (non-distended uterus) helped to dispel thehypothesis that excessive stretching of themyometrium was involved in pre-eclampsia’s etiology[8].

In other words, the uterus is not needed forpre-eclampsia to occur, a fact which was revealed bycases of pre-eclampsia occurring with abdominalpregnancies. Thus AAPs in particular those with livebirths provide a unique and useful opportunity tounderstand certain reproductive biologic phenomena.In addition AAP serves as a prototype of pregnancy inmales, who lack a uterus, however such a pregnancywould be difficult and dangerous.

Methods

PubMed, Scopus and Google Scholar were searchedwith the term ‘advanced abdominal pregnancy’ fromJanuary 1 2008 (the year of the last major review onAAP [1]); the last search date was November 30 2013.



The title and abstract of articles was used to selectarticles that could have a live birth resulting from anAAP (AAP was classically defined). Articles citingthese identified articles were also considered. The fulltext of identified English language articles were read toidentify a live birth resulting from an AAP. Articleswhich had a viable birth resulting from an AAP wereincluded.

A single investigator extracted from the identifiedarticles the variables of year reported, country,maternal age, gestational age at delivery, etc. The fulllist of extracted variables (33) is available in the dataset (see Additional file).

Statistical analysis was done using Stata version 12IC(StataCorp LP College Station, TX).

Continuous variables were tested for normality usingvisual methods namely histograms and inverse normalplots and where the variables were deemed to be notnormally distributed the median and interquartile range(IQR) were reported. A one-sample test of proportion(prtest) was used to compare the proportion of malelive births to the normal proportion of 51.5%; p < 0.05was considered to be statistically significant.

Results

38 cases of an AAP with a live birth were identifiedfrom 16 countries (in Africa, Asia, the Caribbean,North America and South America) see Table 1 andIllustration 3.

The median age of women was 29 years, IQR 24 – 34years. Approximately 50.0% of women were havingtheir first pregnancy when they had an AAP.

36.5 weeks was the median gestation at delivery, IQR33 – 39 weeks. The median birth weight was 2.4kg,IQR 1.35 – 2.85kg.

Of the 32 AAP cases with data on sex of the baby, 12(37.5%) were males.

In 10 (26.3%) cases, the placenta was not removed, infour of these cases a re-laparatomy had to be donebecause of complications resulting from the retainedplacenta. In the remaining 28 (73.7%) cases, theplacenta was either removed completely or partially.

18 (47.4%) of the women received blood or bloodproduct transfusion, but it is important to note that insome of the other cases it was not mentioned whetherblood or blood products were administered.

In 18 (47.4%) cases the diagnosis of AAP was madebefore delivery, in 15 (39.5%) cases the diagnosis wasnot made before delivery and in 5 (13.2%) cases it

was not mentioned or unclear if the diagnosis wasmade before delivery.

30 (79.0%) of the women had sonography beforedelivery, the remainder of the women either did nothave sonography or this information was notmentioned in the articles.

19 (50.0%) cases had an abnormal lie; the lie wasunknown in 16 (42.1%) cases; 10 (26.3%) of the caseshad a breech presentation.

The proportion of live male births of 37.5% had a 95%confidence interval of 20.7% – 54.3%, two-sidedp-value = 0.11.

Discussion

As mentioned earlier, live births from AAP areextremely rare; in recent times nearly 130 millionbabies are born every year [40] yet only 38 live AAPbirths were identified over a period of about five yearsin this study. As has been previously noted in the AAPliterature, the following features were also present inthis study; symptoms and signs of AAP are generallynon specific, an abnormal lie or presentation iscommon, it is difficult to diagnose AAP despite thewidespread use of sonography and there is frequentneed for transfusion of blood or blood products [1].

On average, the sex ratio at birth is 51.5% males [41].The 37.5% male births seen in this study can beattributed to the fact that physiologically males aremore vulnerable than females from conception [42];the presumed hostile extrauterine environment of AAPmay cause excess demise of males compared tofemales. Although in this study some data on the sexof the newborn baby was missing, the sex ratio at birthwould still be in favor of fewer males compared tofemales even if all the missing cases were males.A causal relationship between AAP and excessdemise of males is possible because importantBradford Hill criteria [43] are satisfied, namely strength(37.5% versus 51. 5% males), consistency (in line withthe known biologic fact that males are more vulnerablethan females from conception) and temporality (AAPexposure precedes the abnormal sex ratio at birth).However, it is important to note that there was noevidence that the 37.5% observed in this sample wassignificantly different from 51.5% if p < 0.05 isconsidered to be statistically significant.To the best of the investigator’s knowledge the sexratio at birth has not been previously evaluated withrespect to AAP.



The median gestation and birth weight at delivery werepre-term (< 37 completed weeks) and of low birthweight (< 2.5kg) respectively; this is not unusual for apregnancy in an unnatural location.A case of bilateral [20] and unilateral talipesequinovarus [39] were observed in this study, bothcases seemed to be non-syndromic. Crudely, thiswould yield a congenital talipes equinovarus (CTEV)birth prevalence of 52.6 per 1 000 live AAP births,which far exceeds the estimated CTEV prevalence of1 to 4.5 per 1000 live births [44]. The etiology andmechanism of development of idiopathic CTEV isunknown [44]; one can only speculate about the role ofAAP in the development of CTEV. One infant hadbronchopulmonary dysplasia [38] which was likelyrelated to pre-maturity among other factors [45].Another infant [28] had patent ductus arteriosus,inguinal hernia, undescended testes and phimosiswhich were very likely related to pre-maturity [46].

“The two key components in successful embryoimplantation are the competent embryo and thereceptive endometrium that together undertakeintimate bilateral communication” [47]. Live births fromAAP render this preceding statement debatablebecause the endometrium does not seem to beinvariably essential for successful pregnancy. This hasimportant implications.

It is worth noting that live births from AAP have beendescribed in the setting of HIV infection [17,21],described with twins [37] and one case of abdominalpregnancy diagnosed at 14 weeks of gestation wasmanaged expectantly until delivery at 32 weeksgestation [11].

The key controversy in the management of abdominalpregnancy has been whether to remove or not removethe placenta after delivery [17,20,33]. In this study, inthe majority of cases, the placenta was removedsuccessfully after delivery. Ultimately, removal of theplacenta seems best done on a case by case basis.

Including only English language articles is a limitation,which led to the omission of relevant cases from thenon English language literature for example thisFrench [48] and Persian [49] article. The quality of thereported cases differed, for example some articleslacked information on hemoglobin, the APGAR scoreand other variables which precluded analysis of thesevariables. Some full texts of articles meeting theinclusion criteria could not be accessed, namely thesereports from Ethiopia, Greece and India [50-52]. Areport from Italy not located by the search technique

was omitted [53]. Publication bias is possible whereonly well managed cases were reported. None of thecases mention information about the male partner(father of the newborn); the biologic father isincreasingly recognized to play a pivotal role inpregnancy related conditions [54]. Almost none of thecases where the placenta was removed comment onits gross and microscopic features; pathologicexamination of the placenta in AAP cases can yieldvaluable insights [55].Newspapers remain a valuable source of information[56]; some AAPs with live births have been reportedexclusively in newspapers, here is a selection of AAPnewspaper articles [57-61].

Conclusion(s)

Physiologically males are more vulnerable thanfemales from conception; the presumed hostileextrauterine environment of advanced abdominalpregnancy may cause excess demise of malescompared to females.

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Acknowledgements

I thank Baba and Mai Mpofu for their comments on thenon-technical summary. The images were adaptedfrom Wikimedia Commons the free media repositoryhttp://commons.wikimedia.org/wiki/Main_Page.Thanks to the Stata list for a statistical tip.

Non-technical summary

INTRODUCTIONIn extremely rare cases it is possible for the fetus togrow and develop outside the womb; this is known asan abdominal pregnancy. It is extremely rare for ababy to be born alive after an abdominal pregnancy.These cases where the fetus is in the woman’sabdomen but outside her womb can be caused by thefertilized egg accidentally implanting directly into theabdomen instead of the womb. These pregnanciescan also happen when the fertilized egg wronglyimplants into the tube meant to carry it into the womb,but because the tube is small it bursts and releasesthe fertilized egg which then accidentally implants intothe abdomen. The fetus can also find its way into theabdomen if the womb bursts for some reason. Torepeat, all these scenarios are extremely rare.

WHY WAS THIS STUDY DONE?In the past cases of abdominal pregnancy have helpedpeople to understand some aspects of disease. Forexample, there is a disease that many years ago wasthought to require the fetus to be in the womb for it tooccur. When people saw the disease occurring evenwhen the fetus was outside the womb in abdominalpregnancies, this proved that the womb was notnecessary for this disease to occur. This meansabdominal pregnancies are useful in helping tounderstand certain things. This study was donebecause abdominal pregnancies allow us tounderstand things that we may not otherwiseunderstand.

WHAT DID THE RESEARCHER DO AND FIND?The researcher searched three medically related

databases online that store reports of abdominalpregnancies from around the world. Cases ofabdominal pregnancy where the baby was born alivewere found and from these cases certain informationwas collected such as the mother’s age, the length ofher pregnancy, the sex of her baby, etc.

The researcher found 38 babies born alive after anabdominal pregnancy from 2008 (the last time whenresearcher’s did a similar study) to 2013.

Of great interest was the finding that substantiallyfewer boys compared to girls were born alive followingan abdominal pregnancy. In normal pregnancies(where the fetus is in the womb) on average slightlymore boys are born alive than girls.

WHAT DO THESE FINDINGS MEAN?The findings suggest that more boys compared to girlsare dying before birth in cases of abdominalpregnancy. This finding is consistent with a knownbiologic fact that boys are more vulnerable than girlsfrom the moment of conception (when the spermfertilizes the egg).

That more boys compared to girls are dying beforebirth with abdominal pregnancy is not too surprisingbecause growing and developing outside the womb isharsh and the more vulnerable boys would beexpected not to survive as much as girls.



Illustrations

Illustration 1

Mechanism of developing an abdominal pregnancy. A to D (Secondary abdominal pregnancy), E (Primary abdominal pregnancy).A- tubal rupture, B - rupture of uterine horn, C - uterine rupture, D - fimbrial abortion, E - direct implantation into peritoneal cavity.Note that in cases of AAP due to uterine rupture or a ruptured uterine rudimentary horn, the placenta can remain attached inside oron the uterus



Citation Yearreported

Country Age(years)

Gestation atdelivery(weeks)

Pre-operativediagnosis

Presentingpart/lie

Birthweight

(kg)

Placentaremoved

Sex of baby

[9] 2008 Nigeria 30 40 yes - 3.2 yes Male

[10] 2008 China 30 38 no Breech 3.2** yes Female

[4] 2008 Malaysia - 36 yes§ Oblique breech 3.16** yes Male

[11] 2008 Chile 37 32 yes Breech 1.308 no Male

[12] 2009 India 22 40 no Transverse 3†† yes Female

[13] 2009 South Africa 29‡ 33~ yes - 2.4** yes -

[14] 2009 Nigeria 36 37 no - 2.85** yes Male

[15] 2010 India 22 31 yes - 0.8 yes -

[16] 2010 Bangladesh 36 40 yes - - yes Female

[17] 2010 Tanzania 34 42 no Oblique 2.95 no* Female

[17] 2010 Tanzania 39‡ 33~ no - 2.6 no Female

[18] 2011 Saudi Arabia 23 40 no Breech - yes -

[19] 2011 Ghana 31 38 no Transverse 2.3 partially Female

[20] 2011 Trinidad andTobago

29 33 weeks 4days

yes Breech~ 2.21 yes Female‡‡

[21] 2011 South Africa 29‡ 42 -¶ - 2.6 yes -

[21] 2011 South Africa 29‡ 34 yes¶ - 2.5 no -

[22] 2011 Pakistan 33 39 yes Cephalic 2.4 yes Male

[23] 2011 India 24 37 no Head low 2.4†† yes Female

Illustration 2

Table 1: Selected characteristics of live births resulting from advanced abdominal pregnancies from 2008 to 2013



[24] 2011 Nigeria 20 37 -¶ - 2.65 yes Female

[24] 2011 Nigeria 35 - -¶ - 2.5 no Female

[24] 2011 Nigeria 22 - -¶ - 1.6 yes Female†[24] 2011 Nigeria 23 34 -¶ - 1.7 yes Male

[25] 2011 Bangladesh 29 22~ yes - 1.2†† yes Male

[26] 2012 Nigeria 35 38~ no Longitudinalcephalic

- partially Female

[27] 2012 India 20 38 yes Breech 1.5 no Female

[28] 2012 United States ofAmerica

39 28 weeks 1 day yes§ Transverse 1.205 no Male‡‡


26 32 weeks 1 day no Transverse 1.304** yes Female

[30] 2012 Thailand 33 39 no - 3.49 yes Male

[31] 2012 South Korea 28 34 yes§ Breech 2.1 yes Female


21 25 weeks 5days

yes§ - 0.58 yes Female

[33] 2013 Zimbabwe 33 40 weeks 5days

no Breech 2.85 yes Female

[34] 2013 Nigeria 35 42 no¶ Transverse 3.2 no* Male

[34] 2013 Nigeria 25 35 no¶ Oblique 3.2 no* Male

[35] 2013 Nigeria 20 33 yes Oblique 1.4 yes Female

[36] 2013 India 35 35 yes§ Oblique 1.6** partially -

[37] 2013 Tanzania 24 26 no - T1 0.7 T20.8

no* Females(twins)†


33 24 yes§ Breech 0.66 yes - ‡‡

[39] 2013 Bangladesh 25 38 yes Breech 2.5 yes Male‡‡

Citation Yearreported

Country Age(years)

Gestation atdelivery(weeks)

Pre-operativediagnosis

Presentingpart/lie

Birthweight

(kg)

Placentaremoved

Sex of baby



- not mentioned or unclear, ‡ known to be HIV positive, ~ approximately, § had magnetic resonance imaging , ¶ did not or notknown to have had sonography, ** due to uterine rupture, †† due to ruptured rudimentary horn , T1 Twin 1, T2 Twin 2, * hadre-laparatomy, † early neonatal death , ‡‡ new born had congenital abnormality or complication



Illustration 3

Countries reporting an advanced abdominal pregnancy with a live birth from 2008 to 2013.


live births resulting from advanced abdominal extrauterine ... · live birth resulting from an...

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