Possible Role of Eclampsia/ Pre-eclampsia in Evolution of Human Reproduction
Pierre-Yves Robillard,Gustaaf Dekker,Gérard Chaouat,
Jean Chaline,and Thomas C. Hulsey
Pre-eclampsia is the consequence of a defective implantation of the placenta
that occurs during a critical developmental moment, the second phase of
trophoblastic invasion when the human placenta penetrates even more
deeply into the uterine wall, presumably due to the increased energy
demands of the human fetus. This defect associated with the process of sec-
ondary implantation,as Robillard and his colleagues describe,is one of the
major causes of intrauterine growth retardation. In an attempt to overcome
this failure of implantation, pregnant women exhibit increased blood pres-
sure (gestational hypertension),and the health of both the mother and infant
is threatened throughout the rest of the pregnancy. In extreme forms, and
when undetected,pre-eclampsia can lead to maternal seizures and epileptic
convulsions (referred to as eclampsia),accounting for about 70,000 deaths of
women worldwide. Robillard et al. point out that this type of hypertensive
disorder of pregnancy (HDP) is mostly associated with first pregnancies and,
more specifically, with women who have not sexually cohabited with their
male partners for more than 4 or 5 months. Changing sex partners relatively
frequently is another risk factor for pre-eclampsia. It seems that the longer
the father has exchanged body fluids with the mother,therein exposing her to
his antigens, the less likely this disease finds expression. Researchers
conclude, therefore, that pre-eclampsia should no longer be considered “a
condition of first pregnancy”but more accurately “a condition of first preg-
nancy for a couple”and,thus,a “couples disease.”Robillard and colleagues
propose that selection favored the loss of estrus (sexual periodicity) among
evolving hominins specifically to facilitate more frequent intercourse with
the same partner and,hence,longer exposure to male sperm antigens in the
female reproductive tract. From an immunological and biochemical per-
spective, this behavior reduces the chances of the female’s immune system
rejecting the sperm as if they were foreign invaders, and thus reducing the
chances of eclampsia/pre-eclampsia. In this way, Robillard integrates
changes in male–female sociosexual relationships in the hominin lineage
with increasing brain size, cranial formation in utero, and loss of estrus,
which altogether proposes a new explanation of a significant contemporary
health challenge.
HYPERTENSIVE DISORDERS OF PREGNANCY:
10% OF HUMAN PREGNANCIES
Collectively,the different manifestations of hypertensive disorders of pregnancy (HDP)
represent the main reproductive burden of human reproduction. Notably,this phenome-
non does not occur in other mammals,including primates (Walker,2000). HDP occur in
approximately 10% of human births (approximately 14 million per year of the 136 million
births worldwide [WHO,1999b,2000]).
Besides the abnormally elevated blood pressure in women with HDP, other major
complications can occur,including eclampsia (maternal seizures or epileptic convulsions
that could lead to cerebral injury), which represents, without medical intervention,
0.5–1% of human births (approximately 700,000 per year according to the estimates of
the World Health Organization [WHO,1999b,2000]). More than 95% of cases occur in
developing countries,and they often result in the death of the mother as well as the infant.
Additionally, in 3% of human pregnancies, HDP will be complicated by generalized
endothelial cell disease (“severe pre-eclampsia”) that induces damage to the kidneys
(proteinuria due to a glomeruloendotheliosis) or the liver (the HELLP syndrome—
hemolysis,elevated liver enzymes,and low platelet count). Severe pre-eclampsia,with-
out modern medical interventions,results,in one fourth to one third of cases,in cerebral
vasculopathy and induces epileptic seizures of eclampsia. Finally,in 7% of pregnancies,
women will present with “simple hypertension,”which is reversible after birth. HDP is
the number one cause of maternal deaths in developed countries and number three in
developing areas (after bleeding and sepsis),representing approximately 70,000 mater-
nal deaths per year worldwide out of 530,000 cases (WHO,1999b,2000).
The common thread linking all of the complications associated with HDP is that their
only known definitive cure is delivery of the fetus and placenta by whatever means
possible, including induced labor and cesarean section. As such, pre-eclampsia is the
most common cause of medically induced prematurity. The long-term survival of these
newborns depends on access to resources and knowledge of modern neonatology
(Brown,1997).
Pre-eclampsia is harmful to both the mother and the fetus. Because of poor mater-
nal–fetal vascular exchange, it is the primary cause of intrauterine growth retardation
(IUGR), resulting in increased numbers of babies delivered “small for gestational age,”
or SGA. Throughout the history of humankind, SGA newborns have paid the highest
price of infant mortality (Levene,1985).
In epidemiological terms,HDP are one of the plagues of human reproduction. There
are no naturally occurring animal models of HDP and only a few isolated reports from
primates including Patas monkeys (Palmer et al., 1979) and lowland gorillas (Baird,
1981). These are reports on single cases of epilepsy during delivery and seem to be
218 EVOLUTIONARY MEDICINE AND HEALTH
infrequent when compared to the number of human births associated with HDP. In rare
cases,mammals may present epileptic seizures at delivery because of,for example,hem-
orrhage or hypoglycemia,but these are not the same as HDP.
Eclampsia (maternal convulsions) has been described in humans from different
cultures as early as 4200 years ago (Lindheimer et al., 1999). Eclampsia was probably
interpreted as a curse since epilepsy was associated in all past human cultures with
possession by evil spirits. It is interesting to speculate that our ancestors may have been
able to make the connection between pre-eclampsia and eclampsia,having observed that
young women with edema (abnormal accumulation of liquid in the tissues, one of the
signs of renal dysfunction) at the end of pregnancy were likely to develop eclampsia at
delivery and/or produced tiny newborns.
WHY THIS REVERSIBLE HYPERTENSION DURING PREGNANCY?
Pre-eclampsia is the consequence of a defect in the second phase of trophoblastic inva-
sion (Pijnenborg, 1996; Zhou, 1997). This secondary invasion as a normal part of the
development of the fetus in humans is unique among mammals. The first trophoblastic
invasion occurs at the time of implantation,a few days after fertilization,as in all mam-
mals. In humans, a second invasion occurs 3 months later, after an apparent biological
pause, penetrating deep (as much as one third) into the uterine wall. During pre-
eclampsia,this second delayed implantation is incomplete (see Figure11-1). As a result,
vascular exchanges between the mother and the fetus are severely compromised for the
remainder of the pregnancy. This secondary implantation failure is the major cause of
human IUGR. In an effort to overcome this failure,pregnant women exhibit a hypertensive
response as a compensatory mechanism to try to provide as much nutrition to the fetus as
possible.
The increased fetal nutritional needs at the end of the first trimester result in part from
the increasing energy demands of the relatively large developing fetal brain, and this
increased energy demand may be implicated in the need for the secondary deep tro-
phoblastic invasion. The success of this second,deeper,penetration at 3 months of preg-
nancy may require a significant immunogenetic compromise in terms of paternal–maternal
tissue tolerance when compared to other mammals characterized by a single trophoblas-
tic invasion.
PRE-ECLAMPSIA, DISEASE OF FIRST PREGNANCIES
ALSO A “COUPLE DISEASE”
Complications associated with hypertension in pre-eclampsia and eclampsia are the
result of a global endothelial disease in maternal organisms (Roberts etal., 1989). The
complications are particularly likely among women with predisposition to vascular dis-
eases (diabetes,obesity,thrombophilia). In young women (less than 25 years),however,
before genetic predispositions for these diseases have been expressed, it has long been
observed that HDP most commonly occurs in first pregnancies. It has been well known
for three centuries that eclampsia and pre-eclampsia were “the disease of primigravidae”
with rare recurrence in subsequent ones (Chesley,2000). It has also been recognized for
a considerable time that any kind of previous pregnancy (complete to term,spontaneous
miscarriage or elective abortion) was protective against pre-eclampsia in successive
pregnancies (MacGillivray,1983; Seidman etal.,1989). Pre-eclampsia (and eclampsia)
were also found to be essentially absent in primigravid women who conceived after a
period of long sexual cohabitation (Marti & Herrman,1977).
Pre-eclampsia and eclampsia have been also described in multigravid women with a
short period of sexual cohabitation,such as multigravid women who have changed part-
ners. In both multigravidae and primigravidae,HDP occur in approximately 40% of cou-
ples with less than 4 months of cohabitation before conception, 25% of those with 5–8
months,15% of those with 9–12 months,and 5% of those of more than 12 months (and
the same father in multigravidae) (Robillard etal.,1994,1996). These data suggest that
HDP/pre-eclampsia are not just conditions of mothers,but a “couple’s disease”(Dekker,
1998; Dekker & Robillard, 2005; Robillard et al., 1994). Considering that HDP/
pre-eclampsia is a disease of first pregnancy and that multiparous women with a new
partner have the same risk as primiparous women,it can be concluded that it is the first
pregnancy with a specific partner that is of concern. This recognition is very important,
because pre-eclampsia is no longer viewed as a condition of first pregnancy (primiparas),
but more a condition of “first pregnancy for a couple,”suggesting a paternal–maternal
interaction in its etiology.
Any disease that is more likely to occur in new couples conceiving very shortly after
the onset of their sexual relations suggests that it is very disadvantageous for a human
female to become pregnant on her first ovarian cycles with a new partner. A relatively long
period of sexual cohabitation before conception (at least 6 months) is required to lessen
the incidence of HDP/pre-eclampsia (Robillard etal., 1994). A series of nonconceptive
220 EVOLUTIONARY MEDICINE AND HEALTH
cycles may offer an opportunity for the maternal development of habituation toora tol-
erance of paternal antigens. This is accomplished by sperm exposure,which is essentially
an antigen challenge in the presence of immunosuppressive factors and tolerance
promoting cytokines such as transforming growth factor beta (TGFß) and granulocyte-
macrophage colony-stimulating factor (GM-CSF) (Roberson etal.,2003). This leads to
immune responsiveness and later tolerance to paternal antigens, allowing the deep
secondary implantation of the human trophoblast (Dekker & Robillard, 2005). The
development of maternal tolerance towards paternal specific tissues reduces the risk of
pre-eclampsia in subsequent pregnancies with the same partner. In summary, to reduce
the risk of pre-eclampsia/eclampsia,conception in the human female should occur after
an extended period of sexual cohabitation,regardless of parity of the female,if it is a first
pregnancy for that couple. Interestingly, oral sex (specifically swallowing sperm) is
suspected to be protective (Koelman,2000),whereas using condoms as a regular method
of contraception is a risk factor for pre-eclampsia (Dekker,1998,2005).
WHY A VERY DEEP TROPHOBLASTIC IMPLANTATION IN HUMAN PREGNANCY?:
EVOLUTIONARY CONSIDERATIONS
The very deep trophoblastic implantation in humans suggests that the human fetus
exhibits increased nutritional needs as compared with other mammals. The source of
these increased energetic demands is the human brain. The fetal human brain requires
60% of total maternal nutritional supplies in utero, compared with the 20% demand on
maternal energy in utero in the majority of the 4300 other species of mammals (Cunnane
etal.,1993; Martin,1996).
CRANIO-FACIAL CONTRACTION IN PRIMATES
Since the end of the nineteenth century (Deniker, 1886) and throughout the twentieth
(Anthony, 1952; Biegert, 1936, 1957; Delattre, 1952, 1958; Delattre & Fenart, 1954,
1956,1960; Schultz,1926,1936,1955,1960),it has been noticed that one of the major
evolutionary trends in primate and hominid evolution is an increase in cranial capacity
simultaneously accompanied by cranio-facial contractions. The evolutionary changes in
the base of the cranium were characterized by varying degrees of occipital flexion and
prognathism,depending on locomotory patterns (bipedalism). Gudin (1952) pioneered a
global architectural analysis in the sagittal plane,showing that flexure at the base of the
skull corresponds to the face riding over the frontal bone. This morphogenetic pattern is
found in many living apes and also in the evolutionary phenomenon of hominization. The
three-dimensional organization of basicranio-facial architecture is controlled by the
processes of flexure at the base of the skull,and this affects the morphogenesis of the two
stages of the face,the maxilla and the mandible (Deshayes,1986,1988,1991; Deshayes
& Dambricourt Malassé,1990; Dambricourt Malassé & Deshayes,1992). This phenom-
enon, reviewed by Dambricourt-Malassé (1987, 1988, 1993, 2006), is found in all pri-
mates and in mammals generally. Cranio-facial contraction is minimal in prosimians,
more substantial in monkeys (cercopithecids), even more so in great apes (Pongo,
Gorilla, Pan)and australopithecines (Australopithecus), and maximal in humans. In all
these species,qualitatively,the nature of the process is identical during embryogenesis,
but,quantitatively,it is the embryonic amplitude of cranio-facial contraction that differs
among the various present-day primates.
SHAPE CHANGES IN THE CRANIUM AND INCREASE IN CRANIAL CAPACITY
In recent papers (Chaline, 2003; Chaline etal., 1998; Millet, 1997; Penin, 1997), differ-
ences in the shape of the cranium in some species of great apes,australopithecines,fossil
hominids,and modern humans have been quantified by geometric morphometry (David &
Laurin,1992; Felsenstein,1990; Rohlf & Bookstein,1990; Sneath,1967). For eclampsia
implications it is interesting to link increased cranial capacity in the Homolineage with
ontogeny. The cranio-facial contraction process starts very early in ontogeny,and during
this period,neurons duplicate at the rate of 5000 neurons/second. But this process lasts 2
weeks after fertilization in chimpanzees, for example, while it continues for 8 weeks in
humans. The extension of this period in humans thus brings about hypertrophy (fourfold)
of the brain, and it is interesting to note that the end of this phase corresponds also with
thesecond trophoblastic invasion. Cranial capacity ranges from 282 to 454cm3in chim-
panzees,from 350 to 752cm3in gorillas,from 400 to 550cm3in australopithecines,from
510 to 1600cm3in archaic Homo,and from 1100 to more than 2000cm3in H. sapiens.
According to this view of cranial capacity increase, it is clear that the very deep tro-
phoblastic implantation occurring in humans as a two-phase process may be explained in
terms of increased fetal nutritional needs compared with those in mammals with smaller
cranial capacities. Thus,the appearance of pre-eclampsia in humans seems to be linked
to the development of a large brain in Homo. The most archaic species of the human lin-
eage (habilis, ergaster, rudolfensis, erectus, heidelbergensis, neanderthalensis) exhibit
less cranio-facial contraction and smaller cranial capacity than H. sapiens. The large
increase in cranial capacity observed in H. sapienssuggests that pre-eclampsia could be
a byproduct of natural selection for that trait.
These considerations suggest a new hypothesis for the disappearance of H. nean-
derthalensissome 30,000 years ago (Chaline, 2003; Robillard, Chaline, et al., 2003).
Within the archaic Homobauplan, characterized by reduced cranio-facial contraction
compared with H. sapiens, H. neanderthalensisexhibits the largest increase in cranial
capacity of the group,reaching 1600cm3,a value that falls within the range of variability
of H. sapiens. We may ask whether this large cranial capacity was compatible with
fetal nutritional possibilities at such a primitive stage of cranio-facial contraction and
ontogeny. A hypothetical but possible single-phase process of trophoblastic implantation
may have been inadequate for this large increase in cranial capacity, occurring in an
archaic structure,and this phenomenon may help to explain,at least partially,the disap-
pearance of Neandertals. The two-phase process of very deep trophoblastic implantation
in H. sapiensmay have been an evolutionary solution,a new character,an innovation,or
apomorphy allowing the extended fetal nutrition required by the large increase in cranial
capacity.
222 EVOLUTIONARY MEDICINE AND HEALTH
POSSIBLE BIOLOGICAL CLUES FOR “EXTRAVAGANT”
HUMAN SEXUALITY, LOW FERTILITY OF HUMAN
FEMALES, AND “LOSS OF ESTRUS”IN HUMANS
Among mammals,the human species presents an apparent “extravagant”sexuality:most
human copulations occur at the wrong time to result in fertilization. Copulation takes
place throughout the cycle rather than in a period of estrus, and ovulation is concealed
from male partner(s) and often even from females themselves (Diamond, 1992; 2000).
Further, although extramarital sexuality is ubiquitous in human societies, the human
female does not employ the reproductive strategy of her mammalian counterparts,plac-
ing the sperm of different males in competition at the time of ovulation. Marriage is an
institution in almost all human societies,leading to a longer average fidelity in reproduc-
tive couples than in many other mammalian species (Diamond,1992,2000; Kaplan etal.,
2000). At the same time,the human female displays a rather low rate of fecundity (25%
per cycle at the age of maximum fecundity). It has been calculated that in order to
conceive a human couple needs,on average (albeit there are numerous individual excep-
tions),about 100 acts of intercourse. Demographers calculate a mean time until concep-
tion in couples without contraception of 7–8 months after the beginning of sexual
relations (Léridon,1993). This is unusual compared with the situation of other mammals,
whose sexual relationships during estrus are very fertile. Incidentally,it can be added that
once having conceived, the human female has a somewhat high rate of spontaneous
miscarriage (15%). At first glance,these facts could suggest that the human female is at
some reproductive disadvantage compared to her nonhuman mammalian counterparts
(Léridon, 1993). On the contrary, extensive exposure to the sperm of a particular male
many times before conception (in fact,the life expectancy of sperm being 3 or 4 days in
the female genital tract,even with intercourse twice a week,she is constantly exposed all
the year long—a very rare situation among mammals) and many pregnancies with this
same partner may be a biological adaptation to the risk of pre-eclampsia/eclampsia.
As noted,human females exhibit an unusually low fecundity rate when compared to
other mammalian females. This seeming paradox is coupled with a risk of HDP as high
as 40–45% in new couples with less than 4 months of cohabitation before conception.
Low fecundity and risk of HDP with first pregnancy seems like an unusual reproductive
strategy. Human females are exposed to a roughly 33% risk of HDP in first pregnancies
in societies without modern contraception (Robillard,1999,2002). If,on the other hand,
we experienced a fecundity rate of 75–90%,50% of the first pregnancies (with roughly a
20% incidence of severe pre-eclampsia, and 5% of eclampsia) would experience HDP.
Rather than being an advantage, becoming pregnant quickly after onset of sexual rela-
tions with a partner becomes a disadvantage with respect to pre-eclampsia risk. Thus,a
fecundity rate of 25% seems to be the best compromise between pre-eclampsia in first
pregnancies without threatening fertility for additional pregnancies (multiparity).
Loss of estrus in the human female remains partially unexplained (Pawlowski,1999).
Because of the apparent advantage of a low fecundability rate in humans due to the
reduced risk of HDP, the protective effect of “sexual exposure”with a specific partner
(lost with the absence of constant sexual cohabitation in primigravidae [Robillard,1996])
favored human females who were sexually attractive and receptive across their entire
cycle. The protective effect of keeping the antigens of a specific male partner for successive
births in women (lost in polyandry) induced a minimal rate of long fidelity in couples,
probably not possible in estrus reproduction. The secondary and very deep specific tro-
phoblastic implantation is coupled with the type of placentation, in which there is inti-
mate exchange between maternal and fetal tissues (known as hemochorial placentation;
see Figure11-1). As a consequence, the successful pregnancy requires major maternal
immunogenetic compromises in the face of foreign paternal antigens (Robillard
etal.,2003a,b).
The cumulative net result arising from these various considerations would support the
conclusion that the evolutionary strategy that occurred in humans seems to have been
biased towards paternal tissue recognition through long sexual cohabitation in stable
couples. Human reproductive characteristics that may also be related include loss of
estrus, very low fertility rate, concealed ovulation, non-vulatory sexuality, permanence
of female sexual receptiveness and attractivity,absence of sperm competition in human
females at the time of conception, and relatively large testicle size in human males (see
Robillard etal.,2003a,b).
ETHNOLOGY: BIOLOGICAL, SOCIAL, AND CULTURAL ADAPTATIONS TO PRE-ECLAMPSIA RISK
Infant as well as maternal mortality as a result of pre-eclampsia was a powerful selective
force on the reproductive process of humans. The costs of pre-eclampsia are mitigated by
exposure to the sperm of a particular male partner before a first pregnancy, providing
females the opportunity to develop immunotolerance to foreign cells. This is coupled
with a very low fertility rate and significant incidence of spontaneous miscarriage. In
addition,there are cultural factors that serve to reduce mortality from HDP. For example,
the majority of human cultures encourage marriages of long fidelity in reproductive cou-
ples (Diamond,1992,2000),and the vast majority of human groups prohibit polyandry
(Deliège,1996c). Further,the risk may have been an important contributing factor to the
prohibition of incest in all human cultures (Robillard,Dekker,& Hulsey,2002).
PRE-ECLAMPSIA AS CONTRIBUTING FACTOR IN PROHIBITIONS OF INCEST AND
SYSTEMATIC POLYANDRY
Except for some historical exceptions in royal families (ancient Egypt and Iran,Africa
[Deliège,1996a]),incest has been largely avoided in all human societies. Some anthro-
pological literature states that incest avoidance is neither obligatory,nor properly human,
nor a biological necessity,nor a social necessity. Arguments are that,except for genetic
disorders,incest (i.e.,parents/children,brothers/sisters) may have been a problem in only
1% of births. Even further,some scholars argue that appearance of homozygous deleteri-
ous genes by major incest would be advantageous as a means of getting rid of deleterious
genes in the next generation (Langaney & Nadot,1995).
In our view,avoidance of incest as a means to reduce pre-eclampsia risk may actually
have a biological basis more significant than avoidance of the 1% risk of genetic disorders
224 EVOLUTIONARY MEDICINE AND HEALTH
(Robillard, Dekker, & Hulsey, 2002). Published reports suggest that fertility and preg-
nancy success is greater when parents are not genetically similar. It would appear that,
biologically, females were favored to recognize the father’s antigen as foreign (Grob,
1998). Couples with too similar tissue compatibilities often experienced repeated spon-
taneous abortions (RSAb),and the deleterious role of consanguinity has been extensively
reported (Claman,1993; Hussain,1998; Surendeer,1998; Zlotogora,1997). Furthermore,
after two,three,or four miscarriages during the first trimester,consanguineous couples—
having finally achieved a “successful”pregnancy—experienced a significant increase of
pre-eclampsia (Seidman,1989; Thom,1992). Contemporarily,this RSAb problem (i.e.,
at least three recurrent spontaneous abortions) occurs in very few couples (0.34%) by the
random pairing of histocompatible partners in nonconsanguine populations (Claman,
1993). It would be expected to be much higher in societies where major incest was an
accepted method of reproduction.
Concerning pre-eclampsia, recent data suggest that there is a highly significant
increase of the female-to-male human leukocyte antigen (HLA) compatibility in couples
experiencing pre-eclampsia (de Luca Brunori ,2000),but there are only a few epidemio-
logical reports on pre-eclampsia risks among societies experiencing a high rate of repro-
duction between consanguines (cousins). Brocklehurst and Ross in 1960 (cited in
MacGillivray, 1983) reported in Labrador 10 women with eclampsia in first pregnancy
within an isolated group of British descent with considerable intermarriage across gener-
ations. Among them,five members of one generation from one family married five mem-
bers of one generation from the same family. Of these five marriages, one remained
sterile, and in the other four the women developed eclampsia. Three eclamptic women
were married with cousins in the same family. There were eight cases of eclampsia over
the three generations and three cases of eclampsia with the second pregnancy as well. The
authors concluded that there was an inherited factor for eclampsia transmitted through
the female line. Conversely, Stevenson et al., in 1976 (cited in MacGillivray, 1983),
described a case-control approach to a population in Ankara where consanguineous mar-
riages were frequent. Consanguinity was less frequent in women with pre-eclampsia
(they did not present their results of women by primigravidity and other parities and con-
sanguinity).
It is of note that among 565 cultures described (Deliège,1996b),only two polyandric
cultures have been reported:the Toda in southern India and the Nyinba people in Nepal
(Deliège,1996c). Interestingly,in these two groups,polyandrous unions occurred oblig-
atorily, with brothers of the same family (adelphic polyandry) marrying the same wife.
Conversely, inside the small high caste of Nayars in Kerala, South India, reproductive
unions occurred with apparently total free polyandry. In addition to explanations of low
polyandry as a means of ensuring male parental care or patriarchal control of women’s
fertility,an absolutely free systematic polyandry might have been noticed to contribute to
higher pre-eclampsia/eclampsia risk and thus lower fertility.
ETHNOLOGICAL ASPECTS
Because of the importance of eclampsia in humans,ethnographers should be able to collect
information on different human interpretations concerning convulsions and pregnancy.
The association between delivery and seizures should be recorded in one way or another in
human memories (e.g.,in myths,tales,songs). Cultural development of morals of these sto-
ries should be very instructive with regard to their interpretations of convulsions in child-
birth. Particularly, it would be interesting to investigate whether this “curse”is directed
toward the mother only or toward the couple. If the latter is the case,it may be that past cul-
tures had noticed facts that modern medicine has taken a long time to rediscover.
CONCLUSION
HDP, and especially pre-eclampsia, are frequent in both the developing and developed
world. In developed areas,hypertension is often associated with kidney or liver injury,and
hospitalization is usually recommended. In case of threatening signs of eclampsia (mater-
nal convulsions), the only treatment is to perform an emergency cesarean section and
deliver the fetus and the placenta. This is a frequent concern of obstetricians and neonatol-
ogists and has implications for epidemiologists,biologists,immunologists,demographers,
anthropologists, palaeoanthropologists, ethnologists, geneticists, zoologists, and others.
Many of these disciplines have not been traditionally included in discussions of HDP.
The authors of this chapter are not aware of any ethnographic report of eclampsia or
its associated convulsions and high mortality, notwithstanding that this is a common
human reproductive complication factor with both biological and cultural implications.
We encourage ethnographers to engage women, sorcerers, shamans, and other healers
with the simple question:“What is the meaning of a young woman dying with convul-
sions giving birth?”Responses should give some clues of the extent to which this prob-
lem is known across cultures.
Further research to describe the biological pathways explaining the global reversible
endothelial inflammation that is encountered in women presenting pre-eclampsia/
eclampsia (Roberts etal.,1989) and the mechanisms of the paternal–maternal immuno-
logical conflicts leading to the poor implantation of certain human trophoblasts (Chaouat
etal.,2005,Dekker & Robillard,2005) is required. At the beginning of this twenty-first
century,there are some hopes that these biological clues can be finally fully understood
within one or two decades.
For zoologists, anthropologists, and others working in comparative reproduction,
knowledge of hypertensive disorders of pregnancy may give clues to understanding cer-
tain features of human reproduction,including the two-wave implantation of the human
trophoblast,the very low fertility rate of human females,loss of estrus,concealed ovula-
tion,“continuous”sexuality,absence of sperm competition in human females at the time
of ovulation,relatively large testicle size in human males,prohibition of incest,and low
frequency of systematic polyandry in human cultures (Robillard etal.,2002,2003a,b).
If it is true that the “two-wave”process of implantation of the trophoblast is unique to
humans, palaeoanthropologists may hypothesize that the appearance of pre-eclampsia
during hominization may have arisen at a point in human evolution that brain mass of
Homofetuses increased to a critical point. Perhaps HDP can even help to explain the
disappearance of the Neanderthals (Chaline,2003).
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