Synchronic and Diachronic Investigation of the Long-Term Effects on
Reproductive Health of Heavy Metals, Environmentally Stable
Military Remnants in Gaza, Palestine: A Summary
Paola Manduca
Newweapons Research Group, Genoa, Italy
Keywords: Heavy Metals, Weaponry, Chronic Human Contamination, Reproductive Health Outcomes.
Abstract: Here is reported research “on the other side of weapons”, that of the victims, aiming to diffuse knowledge of
the long-term damages to health by heavy metals in weaponry, invisible and stable war remnants in the XXI
century wars. The work reported is exemplary in identifying at each time point (synchronic approach) and
along 13 years (diachronic approach) the source of heavy metal contaminants in weaponry, their chronic
uptake by humans and proving association of exposure to attacks and metal contamination with reproductive
damage in the war setting of Gaza Palestine. Many heavy metals found in weaponry are toxicants, fetotoxic
and carcinogens, are spread indiscriminately by ammunitions, are stable in the environment, suggesting that
their use in attacks on civilian areas falls under more than one prohibition by international law. To date, we
are not aware of other studies of surveillance of reproductive health in any war area on a wide random cohort,
nor of this being accompanied by systematic parallel investigation of human contamination by heavy metals
delivered by weapons, white phosphorus shells, and in wounds by not-fragmenting ammunitions. The data
altogether, allow comparison among time points (diachronic view); this view allowed to understand the entity
of the long-term effects of metal contamination of mothers on birth outcomes, the persistence of these effects
vis a vis the environmental contamination, to single out and confirm which of the many metal elements found
at high levels in post-war area is affecting negatively the outcomes at birth, and to describe long-term impact
of recent war events on health, before and after displacement of war remnants. It documents that one of the
tolls by war-remnant heavy metals contamination is increase of deaths in the perinatal age, “invisible war
victims”.
1 INTRODUCTION
These investigations focused on the role of heavy
metals, fetotoxic and carcinogenic or toxic for
mammals, and “invisible stable weapons remnants”
of war, and on their role as effectors of negative
reproductive health outcomes.
Heavy metals, components of many weapons
systems of this century, which Israel used on Gaza,
do not disappear from the environment, and have the
potential to cause, by various mechanisms, long-term
health damages upon acute and chronic exposure and
via accumulation in organs (Domingo, 1994; AIRC,
2020; ATSD, 2011;
Rice, 2014; Amadi, 2017;
Wai,2018; Rahman, 2016; Cheng, 2012; Grandjean,
2105; Bommarito, 2017).
Military aggressions and wars draw an almost
continuous line of fire along the last 23 years, from
Yugoslavia through Southwestern, Western and
Central Asia, Middle East, and north Africa.
Although the impact of stable war remnants is a
concern in each of these places of war, there are only
sporadic scientific reports about these stable
chemicals, heavy metals delivered by weaponry, in
association with negative outcomes of reproductive
health of populations.
To investigate the changes in reproductive health
associated to contamination of a population by stable
effectors as heavy metals delivered by weaponry,
poses many challenges of various nature.
Daunting ones are the lack of specific biomarkers
of their biological effects, the scarce knowledge about
the mechanism of action of heavy metals, and the
complexity due to the compresence of several heavy
metals in the war-remains. Much more work is
necessary to tackle these aspects.
Manduca, P.
Synchronic and Diachronic Investigation of the Long-Term Effects on Reproductive Health of Heavy Metals, Environmentally Stable Military Remnants in Gaza, Palestine: A Summary.
DOI: 10.5220/0012007300003536
In Proceedings of the 3rd International Symposium on Water, Ecology and Environment (ISWEE 2022), pages 243-255
ISBN: 978-989-758-639-2; ISSN: 2975-9439
Copyright
c
2023 by SCITEPRESS Science and Technology Publications, Lda. Under CC license (CC BY-NC-ND 4.0)
243
Some wars are ongoing, posing difficulties in
access. Others have been very long, and even after the
wars, there have been “intrinsic” factors hindering
adequate design for systematic studies, e.g., the
displacement of populations and/or the concomitance
of other crisis also potentially impacting health, lack
of previous birth registry to use as reference.
There was also decisive hindrance by “extrinsic”
factors, local governments, or external occupiers,
opposing to the documentation of long-term effects
on reproductive health potentially due to the
weaponry used and to their remnants, because this
documentation could imply responsibilities for
having used these weapons in wars waged extensively
on the civilian populations. Thus, local, and
occupying authorities took unhelpful, or at time
threatening, postures against the research, even when
collaboration was sought by local professionals;
international health bodies, when intervened, often
did not publish the results in scientific journals with
review.
In Gaza, aside minor events, the research work
was accepted and facilitated by the local authorities,
the UN bodies in the field, and by highly
collaborative professionals. What is presented here is
the result of a collective effort.
In Gaza the “intrinsic” conditions allowed to
adopt a satisfactory scientific design; paradoxically,
the inhuman siege contributed to make easier some of
the aspects of the research, since it forced people to
residential stability, thus defining the length of post-
war chronic exposures to war remains and allowed to
trace the chronology of the removal of ruins and war
remnants.
Positive “extrinsic and intrinsic” conditions in
Gaza allowed to persevere in the investigations for 13
years, for what is an unprecedented span of time in
any war area, although with interruptions due to the 3
wars waged on Gaza meanwhile (2009, 2012, 2014).
Nonetheless, the recurring attacks with varied set of
weaponry posed and extra challenge to the
interpretation of data.
Anyhow, it was possible to acquire reiterate
extensive synchronic information through surveys at
birth and parallel analytical data of metal load in
women and newborns, and to include verified recall
of exposures to potential environmental sources of
heavy metals; repeat of the surveys and assessments
in time, having developed and used the same standard
methodology for acquiring data along the years,
allowed to compare diachronically the sets of yearly
data.
The investigation in Gaza covered the span of the
years 2006- 2019. It started documenting the delivery
by weaponry of heavy metals, and its assumption by
the population. It involved studies of human
contamination by heavy metals in random cohorts.
One of them was of 95 children; 5 were cohorts of
women delivering a baby, for a total of 14.000
women, including some exposed at different and
multiple times to major military assaults by the Israeli
army. The survey of the outcomes of birth involved
about 13.500 women, in 4 cohorts.
The studies also collected, through collaboration
with UN and local environmental and agricultural
authorities, analytical and historic details of the
environment and of usage of chemical in civil life,
obtaining a body of circumstantial information,
including that about the localization of military
attacks which confirmed women’s recall of exposure
to these attacks. Together, this extended consultancy
surrogated the interpretation of association of heavy
metals in weapons remnants as effectors of
reproductive health and helped to understand the
timing and circumstances that caused the diffusion of
these effectors in the environment.
The research developed stepwise; each step
motivated by the results of the previous one and
incorporated the novel questions that these posed; it
resulted in obtaining eventually a picture of the
environmental contaminants delivered by weapons,
of the pattern of their assumption by civilians under
acute and under chronic exposures and of the
correlation of the assumption of heavy metals by
women with their reproductive outcome.
Rare sporadic reports, and our own unpublished
data from other war areas suggested decrease in
reproductive and whole health in people residing in
locations militarily attacked, and, in some cases,
reported human and environmental contamination by
heavy metals.
A word will be spent on the potential use for the
information presented here.
2 METHODOLOGIES
Multiple sources of information were used, various
scientific tools and different methodologies
appropriate to cover each sector of the investigations
and these were published (Skaik, 2010; Abed, 2014;
Naim, 2012; Manduca, 2011, 2013, 2014, 2019;
Baraquoni, 2020; Vänskä, 2019).
The research involved field work, environmental
assessments, and hospital-based work with local
professionals as partners and consultants and
analytical measures were done abroad certified labs,
the same since 2011.
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Protocols were prepared for each step of the
work: adequate collection for the analysis of inert and
biological samples, clinical and environmental data
recording and preservation of biological samples for
analytical studies.
Inert samples from bombed sites or ammunitions,
were used to investigate the presence of heavy metals
in weapons used in Gaza. Hair was collected of 4cm
length at the nape for adults. The appropriacy for
analytical studies on formalin preserved biological
samples was also tested.
The amount of 23 heavy metals in inert materials,
hair and in biopsies of the wounds was determined by
Inductively Coupled Plasma Mass Spectroscopy
(ICP-MS) in 2 certified laboratories in Italy and in
Canada. All hair samples of women and babies were
analyzed in the same laboratory which legitimizes
comparisons. In all the analysis appropriate controls
were utilized. E.g. for inert samples, the soil from
outside the crater zone; for biopsies, layers of the
tissue at a distance from the wound from the same
individual; for hair, adult controls were from
individuals from countries outside the war area and
for newborns the hair of normal Gaza’s babies.
Detailed protocols for collection of participants
consensus and hair samples, questionaries for
registration of data at birth from mothers included
questions on mother’s historical health records,
parity, prenatal prevention care and provider,
nutrition, medication and habits, marriage with first-
and second-degree relatives, but also health records
for the other children of the couple, and for the
parents’ extended family, data on child sex, living
parameters, clinical diagnosis, singlet or twin, type of
delivery. The questions on exposures to possible
toxicants/teratogens in civil life (8), on military
events exposure (15 or more), about the state of the
dwelling and rubble reuse after wars (4) were updated
after each new war to account for the changes in the
environment.
3 RESULTS
3.1 Chronology of Military Attacks
The temporal context of the major attacks in Gaza is
shown in Table I with the extent of damages since
2008.
Table 1: Chronology of the major military attacks on Gaza
before 2021, number of victims/damages.
The attacks reported here followed a shorter but
intense one in 2006, when were used for the first time
weapons that caused wounds without fragments
strikingly like those reported at the same time in the
contemporary war to Lebanon. Call for help to
understand the strange wounds that were presented
with in these attacks, issued by doctors in these two
countries to professionals abroad, and their reports of
unexpected prognosis after care for these previously
unseen wounds, together with the published
information of the development by US firms of metal-
augmented weaponry, and the acknowledgement by
Israel of “field testing” novel weaponry, triggered our
research “on the other side” of weapons.
3.2 Heavy Metal Remnants Delivered
by Weapons in the Environment
and in Wounds
Craters and WP ammunition were tested for the kind
and load of heavy metals and were shown to delivery
fetotoxic and carcinogen metals (Table II).
Table 2: Qualitative summary of content in heavy metals,
among the 23 tested, which were found in fivefold or more
amounts compared to controls. Al - aluminum, Hg -
mercury, W - tungsten, Mo - molybdenum. WP = white
phosphorus. Yes >5 fold than control.
The craters tested were produced in 2006 and
2009 by heavy bombs that made wide and deep holes
in land. In 2009, 3500 WP shells, each spreading its
content for a radium of 300m, were used on Gaza,
potentially covering with their content 1/9 of the
surface of the Gaza strip.
Biopsies at the site of wounds caused by weapons
without fragments, including White phosphorus
burns, were collected, and tested for their metal
Synchronic and Diachronic Investigation of the Long-Term Effects on Reproductive Health of Heavy Metals, Environmentally Stable
Military Remnants in Gaza, Palestine: A Summary
245
content, as proof of fact that the weapons that had
produced them delivered heavy metals.
Tissue from 15 victims was analyzed. Each
wound was clinically classified by surgeons. Wounds
within the same group of clinical classification had
similar content and quantity of metals, while wounds
in clinically different groups had a different specific
metal signature.
Figure 1: Wounds from victims in 2006 and 2009 from
which biopsies were analyzed by ICP/MS.
In Fig 1 is shown the kind of damage inflicted to
the victims and the clinical classification of wounds,
and in Table III the comparison of the load of heavy
metals detected in the tissue from each clinically
different kind of wounds.
Table 3: Qualitative summary of metal load in clinically
different wounds and date of the wounding. Cd-cadmium;
U- uranium; V-vanadium; Sr-strontium; Cu-copper; Ba-
barium; Sn-tin. Yes highlighted in green > 5fold than
control; yes highlighted in blue >2 fold than control.
The data are proof of fact that weaponry without
fragments each delivered heavy metals, and that the
metal signature was specific for the different clinical
damages inflicted.
3.3 Human Intake of Heavy Metals
Delivered by Weapons
Testing the hair of 95 children for the load in 23
metals 8-9 months after the attacks in 2009, showed
that 60% of them had higher load in the hair grown in
the last 3-5 months for all the toxic metals reported in
Tables II and III than control children living in 2
towns in Italy and 1 town in Israel, and of the
standards load form other not war areas (not shown).
This finding implied that was ongoing human
contamination by metals delivered by weaponry and
signaled chronic intake by a wide segment of the
population, alerting to the possibility that high level
of contamination of humans might affect their health
for a long time, and might negatively interfere with
pregnancy, embryo, and fetal development.
3.4 Changes in the Prevalence of Major
Structural Birth Defects Bridging
War- Retrospective Approaches
Aware of the potential risks of heavy metal
contamination for reproductive health, two
retrospective approaches were used to assess if there
had been changes in prevalence of major structural
birth defects (BD) in the time bridging the 2009 war:
analysis of data retrieved from registers of all
pediatric hospitals in Gaza (Table IV), and
reconstruction of BD incidence in the history of more
than 40 families with a normal child born in 2011
(Fig.2).
From the records of the pediatric hospitals in
Gaza was calculated the prevalence of major birth
defects occurring at two time points, in 2006 and
2010, spanning the military attacks in 2009 (Table
IV).
Table 4: Prevalence of BD among 0-2 years old children
registered in all Pediatric hospitals of the Gaza strip in the
first six months of 2006 and 2010.
Increase (p<0,001) in 0-2 years old patients with
BD occurred spanning the attacks in 2009.
Collecting from parents the self-reported events
of BD in their progeny and the date of birth of all their
children, is possible to reconstruct the frequency of
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BD in the progeny as they occurred in time (Figure
2).
Figure 2: Increase in time (1997-2010) of the frequency (%)
of major malformations in families with a normal newborn
in 2011 and with a previous child with birth defect.
Sp=sporadic, Fam=documented familiar. Cochran-
Armitrage trend test for Sporadic malformations p<0.001,
for familiar malformations p=0.59.
The prevalence of BD increased in time between
1997 and 2010; those BD for which there was not
documented familiarity contributed disproportionally
to the overall rise, supporting the hypothesis that
environmental effectors affected the incidence of BD
and that these effectors were introduced between
2006 and 2010.
The two independent retrospective approaches
showed the increase in prevalence of BD bridging the
2009 war. The two approaches concur to signal
increase in BD after the major war in 2009.
The reconstruction approach sets the starting time
of the increase to the first campaigns of airstrikes on
Gaza; these started in late 2005 as soon as colonial
settlers left the Gaza Strip;
3.5 Association between Mother’s
Exposure to Attacks, Progeny
Outcome, and Metal
Contamination in Newborn Hair
A survey at birth was conducted to establish if there
was a correlation between the exposure of women to
attacks and their probability to have a baby with BD,
and if the BD babies had a higher load in heavy metals
than normal babies. Survey at birth was implemented
in Gaza in 2011. Data of a random cohort of almost
3000 delivering women were collected in sequence in
one Maternity. In the registration questionnaire
included questions about exposure of the mother to
potential negative effectors of health (habit to smoke
tobacco or shisha, use of drugs, use of chemicals,
nearness to/work in industrial and agricultural areas
and exposure to previous military attacks) and
historic residence of the couple.
In this cohort of women those that recalled being
under bomb and/or WP attacks in 2009 had with
significant higher frequency newborns with BD,
compared with women not exposed to attacks
(p<0.001) (Table V).
Table 5: Correlation of the mother exposure in 2009 to
attacks, by kind of weaponry, with the prevalence (%) BD
in their progeny born in 2011.
Recall by mothers of their exposure to military
attacks was verified, crossing the address of their
residence with the place and kind of ammunition used
in attacks, on the maps recording military attack,
accessed by courtesy of the UN Mine Action Team.
The hair of newborns in the cohort was collected
within 5minutes from delivery, metal load was
measured, and the results indicated passage of heavy
metals in utero.
Comparison of the load of heavy metals in BD
versus normal babies, showed significant higher
amount of mercury (p<0,003), tin (p<0,002), and
selenium (p<0,004) in BD newborns than in normal
babies. Preterm babies, also tested, showed a different
pattern of contamination than BD and normal
newborns, having higher load in barium (p<0,03) and
tin (p<0,002).
There was correlation between mother exposure
to weapons, negative outcome of pregnancy, and
higher load of heavy metals in BD or preterm
newborns hair than in normal babies. The
contaminants in highest load were specific: mercury
and selenium for BD and barium for preterm.
The association of these specific metals in high
load respectively in BD and preterm, is consistent
with what is known respectively about the teratogenic
effect of mercury, and the synergism in teratogenicity
of high loads of selenium with mercury, and about the
toxicant effect during pregnancy of barium.
The association: mother exposure to attacks-
negative birth outcome-high load in specific heavy
metals was found almost 2 years after the women
were exposed to the attacks in 2009, implying long-
0
10
20
30
40
50
60
1997-1998 1999-2000 2001-2002 2003-2004 2005-2006 2007-2008 2009-2010
%Sp/TOT %Fam/Tot %BD/tot
Synchronic and Diachronic Investigation of the Long-Term Effects on Reproductive Health of Heavy Metals, Environmentally Stable
Military Remnants in Gaza, Palestine: A Summary
247
term effects of an event of acute contamination and/or
effects due to long resilience in the environment
where heavy metals war-remnants remained, and
ongoing chronic contamination. It is compatible with
the second possibility the fact that these women, in
the large majority of cases (90%) continued to reside
in the place where the attacks had occurred, and
remains of weaponry remained in or near their
housing.
3.6 Recent Exposure to Military
Attacks Increased the Load of
Heavy Metals Above a High
Background in a Cohort of Women
and Their Newborns
In early 2015, was assessed the extent of women
contamination in relationship with recent exposure to
weaponry of a cohort of 502 women, who were 1-3
months pregnant during the attacks in 2014. 70% of
the women recalled exposure to the recent attacks on
their housing; their recall was verified in 108 random
cases, and damages to their housing was confirmed in
99% of the cases by photos.
Hair from the mothers and their newborns was
tested for metal load, reflecting the last 4 months of
accumulation in mother and the whole fetal life in the
newborns. It was found positive correlation between
proximity of the mothers to military attacks and a
higher load of toxicants (Ba, Al, V, Sr, Cd and Cr),
teratogen (Hg, W) and a carcinogen (As) compared to
women not exposed to attacks (30% of the cohort).
There was no difference for the concentration of
microelements (Cu, Se, and Mo).
Trans-placental passage occurred for heavy
metals from mothers to their newborns, the median
metal load of the babies being much lower than the
mothers' load.
Of relevance, the samples of hair from these 502
Gaza women had higher 95 percentile values of
concentration compared with a standard control of
hair from individuals the outside war area (Table VI)
for heavy metals of relevance for health and identified
as weapon remnants also from previous attacks, in
2009.
Table 6: 95percecntile of the load (ppb) of 23 metals in the
cohort of 502 mothers that delivered in 2015, compared to
standard controls (in red). Highlighted in blue are the metals
with values higher for women in Gaza than for the controls,
column on the right indicate the p value for the comparison.
Molybdenum, selenium, tin and titanium showed no
significant difference from controls.
These data point to a high background of already
existing contamination by weapon remnants and to
chronical assumption, to which the recent attacks
added quantitatively.
3.7 Birth Registry and Prevalence of
Negative Outcomes at Birth, from
2011 to 2019
Comparison of birth surveys taken in different years
was possible because the same methods, procedures,
and randomness of the cohorts, was used. It showed
that further increase in the incidence of birth defects
and preterm babies occurred from 2011. The increase,
between 2011 and 2016, bridging 2 wars in 2012 and
2014, was very significant; prevalence values did not
change significantly after 2016.
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Table 7: Comparison of the incidence of negative birth
outcomes (%) in surveys in 2011, 2016 and 2028-2019. In
each of these years respectively 2940, 6104, 4707 deliveries
were registered in sequence. Preterm, born before 37 weeks
of gestation age; BD, birth defect. N is the number of cases.
Highlighted in blue, the p values of significant differences
in incidence between years.
For BD the change in prevalence was not
associated to increase in intermarriages, which
instead decreased since 2011. The increase in BD
between 2011 and 2016 was substantial in such short
time, and so was the contribution of sporadic novel
cases, deduced in the basis of the family history, also
collected in the survey. The change of the prevalence
in preterm is extremely relevant and compatible with
being induced by chronic exposure to metal
contaminants in the environment which likely
accumulated during the two wars in 2012 and 2014).
3.8 Assessment of Exposures, Metal
Load in Mothers in Relation with
Outcome of Pregnancy, Years
2011-2019
In the 6-9 months after the attacks in 2014 the load of
metals in mothers exposed to them was higher than in
not exposed. Between 2015 and 2019 there were no
major new military attacks on Gaza.
The two major military attacks in 2012 and 2014
were accompanied by extensive destruction of
housing and infrastructures and, following these
attacks, clearing of the debris and reconstruction had
to wait years to be done, due to lack of machinery and
cement imposed by the blockade by Israel and, since
2013, also by Egypt.
Cleaning up started in middle 2016, involved
removal of the rubble of destroyed buildings and
infrastructures and its reuse through pulverization of
the debris in open air and disposing of the biggest
chunks by or into the sea.
Before this time, the rubble remained largely in
the proximity of hit buildings and infrastructures, in
the roads and fields, available to be washed out and
dispersed by flood rains and enter the (still) open
sewage. In 2016, 34% of the cohort of mothers in the
survey resided near open sewage or garbage mounds
also containing remnants of the destructed structures.
The significant increase in BD and preterm births
in 2016 compared to 2011, had no correlation with
previous exposure of the mother to attacks in 2014
(43%). Rather, having babies with BD was
significantly associated with nearness of the
residence to places where garbage was burned in open
air, and having BD and preterm babies were
associated to residence near to open sewage, as shown
in Table VIII.
Table 8: Percentage of mothers residing near risky locations
and recalling exposure to attacks in 2014, in relationship
with the outcome of their pregnancy.
The cohort of mothers which resided in proximity
to military remnants had also significantly higher load
of toxicants in their hair (Ba, V), teratogen (Hg) and
carcinogen (Co), compared to those leaving far from
these sources of contaminants (Table IX).
Table 9: The heavy metals whose load in mothers’ hair was
higher for residents near sewage and open burning of
garbage that in the hair of those not near.
Thus, in 2016 there was correlation between
woman residence near risky deposit of war remnants,
higher probability of having a BD or preterm baby
and their higher load of contamination by specific
heavy metals.
In the survey of births in 2018-19, no correlation
was found between mother’s exposures to previous
military attacks with the metal load in their hair or
with the outcome of pregnancy. In 2018-19 only 12%
of the mothers still lived near war remnants.
Nonetheless, the prevalence of negative outcome
at births did not decline from 2016 and the
95percentile values of concentration of the heavy
metals, concerning for their toxicity or impact on
health, were consistently higher than those of
references, and, for most, similar as in the previous
years (Table X).
Synchronic and Diachronic Investigation of the Long-Term Effects on Reproductive Health of Heavy Metals, Environmentally Stable
Military Remnants in Gaza, Palestine: A Summary
249
Table 10: The 95 percentile values of the metal load of 12
toxic metals in the hair of the women in the cohorts
registered in the years 2015-2019 compared to reference
samples (in red). Highlighted in blue are the values
significantly higher in the cohorts tested than in the
reference control. For titanium and arsenic the 95percentile
values become higher than control only since 2016.
Comparison of the median values of the load of
these metals in women in time (Table XI) is more
reflective of the diffusion in the population than the
95percentile values. Median values showed
significant increase from 2015 to 2018-19 for some
of them As, Cd, Co, Cr, Sr, Ti, U and V (highlighted
in pink); decrease, only in 2018-19 for Hg and Mo,
and decrease since 2016 for Se (highlighted in green);
the level was unchanged for Ba.
Table 11: Comparison of the median metal concentration in
hair of cohorts of mothers in the years 2015-2019.
This data confirms the patterns seen in comparing
95percentiles values, the resilience of these metals in
the environment and the continuing assumption by
the population in the post-war context up to 5 years
from the last military attacks. They also confirm the
increase above the control values of titanium and
arsenic only from 2016.
The lack of correlation between mother exposure
with birth outcomes in 2018-19 is compatible with the
wider spread of heavy metals in the environment
during the disposal of war remains that made them
equally available to all. Chronic and diffuse exposure
to the environmental toxicants flattened the
differences in metal loads due to previous recent or
locally confined sources of exposure. The wider
spread of contaminants in the environment
"equalized" and stabilized at a high level the
stochastic chances of negative events occurring
during pregnancy
Analysis of the subgroup of newborn with birth
defect in 2016 showed the presence of a higher load
of titanium in their hair than in those of normal or
preterm babies. Titanium, and Arsenic 95 percentile
values were not different that control in the cohort
tested only 6-9 months after the attacks of 2014, but
their 95percentile values increased since 2016; the
median values for Ti increased in 2016 and median
values for As in 2018, as shown above in Tables X
and XI.
In 2016, there was association of BD newborn
with higher load in titanium than in the group of
preterm babies, and with a slightly higher load in
mercury, as previously found in 2011; preterm babies
had higher loads than normal babies for a number of
metals, noticeably including barium.
Table 12: Metal load in newborn hair in the year 2016 total
sample is 60. Amounts in ppb are shown, for BD and
preterm newborns and these are compared to each other and
highlighted, in yellow= more than 2 fold, in grey more than
1,5 folds.
In 2011 the value in ppb amounts of mercury (0.93
ppb) was higher than in 2016, but in both years was
higher than in normal and preterm babies. The value
of barium amounts in preterm babies in 2011 and
2016 were similar (1,07 and 1,09 ppb). Tin was much
lower in 2016 in BD babies and for preterm babies,
compared to newborns in 2011.
Cadmium amounts did not change in time, while
chrome levels were 1,5 folds higher in 2016 than in
2011 only in preterm babies. Other metals tested 2011
did not differ in preterm or BD in their loads from
normal babies.
These data suggest that, while there is consistent
high load for some metals associated with BD or
preterm outcomes, there may also be a difference in
kind or/and amount of each metal in the weapons
remnants from each successive war, that can also
affect the negative outcomes at birth.
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4 DISCUSSION
To date, no study has been produced of surveillance
of reproductive health in any war area on a random
cohort of relevant size accompanied by systematic
parallel investigation of human contamination by
heavy metals delivered by weapons and by objective
verification of individual's exposures to war-related
events, or of newborn contamination by heavy metals
related to the kind of negative outcome at birth.
Also, there was no previous proof of fact and
characterization of heavy metals delivered in the
wounds by white phosphorus ammunitions and by
not-fragmenting ammunitions, both weapons used in
Gaza.
The main points of force and the novelty of the
study are the consistent methodological approach of
its design and data collection, its time frame allowing
diachronic vision of the data, the multidisciplinary
sources of information from which it draws.
Lack of these elements in previous reports, may
be due to the limitations posed, by intrinsic and
extrinsic factors, to investigations in a war or afterwar
area.
4.1 Methodology in Data Collection
and Multidisciplinarity
Methodologically, epidemiological studies on
random cohorts of size adequate to the questions
investigated, are the best if not the only way to
eliminate biases. The elaboration of an appropriate
questionnaire for birth survey, inclusive of
environmental questions focused to the contemporary
local context, in addition to the Eurocrat or WHO
format, allows to ascertain synchronically the
contribution of diverse environmental factors to
reproductive health, and measure of metal
contamination on the same random subset of
population in which the epidemiologic outcomes are
registered allows correlations between the two sets of
information.
Methodologic consistence made possible to
compare, diachronically, different sets of birth
surveys and epidemiologic data, including the
objectively verified recall of exposures by the
individuals, and of measures of contamination by
heavy metals.
The knowledge of the environmental situation and
of its changes in time has been most valuable.
Consultation with experts in other fields allowed to
acquire knowledge often neglected or unavailable in
this type of investigations, which proved very
valuable for integration of the questionaries of survey
in the course of the work, for validation of subjective
recalls, and for interpretation purposes.
The knowledge of the precise chronology of the
attacks and documentation of their places, and often
also of the weaponry used, allowed the validation of
recall of exposures by the women; that of the
modalities of disposal of debris and of the length of
time till they were unremoved, the modalities of
recycling and places where it occurred, and the
damages in the infrastructures, the lag in
reconstruction, have been important factors for
interpretation of the data in this study. The
multispecialty collaborations also made possible to
prove the delivery by weaponry to the ground in Gaza
of defined heavy metals, and to give proof of fact of
which of these metals are delivered in wounds.
The possibility we had to use a diachronic lens
proved important for interpretation of data. It was
very exceptional to have the privilege to pursue these
studies along many years and with many colleagues
in Gaza.
4.2 Summarizing and Concluding
The heavy metals delivered by various weaponry
were identified and, in the limited types of
ammunitions tested, were detected carcinogen,
fetotoxic and toxic metals. In the case of metals
embedded in the flesh at the site of the wound, they
imprinted a molecular signature different for each
type of clinically classified wound. Also white
phosphorus ammunition delivered heavy metals in
the wounds.
Nine months from the attacks in 2009, heavy
metals were found in the hair of 60% of children in a
random cohort covering all the Gaza strip.
At least since the first time they were tested for, in
2010, heavy metals delivered by weapons in the
environment were assumed by the population, and
since then there has been chronic exposure to war-
remnants of the civilians. The level of heavy metals
contamination in the population was shown to
increased immediately in the individuals exposed to
the 2014 military attack.
The measure of metal load in random cohorts of
women in Gaza showed all the time that were tested
since 2011, a higher 95 percentile value for metals
associated to weaponry, by comparison with the
reference, controls from outside the war area.
Molybdenum instead was always lower than controls
and titanium concentration increased over the control
only in 2016. A similar pattern was found comparing
in time of the median values of metal loads, thus
ruling out the eventual relevance of spike values,
Synchronic and Diachronic Investigation of the Long-Term Effects on Reproductive Health of Heavy Metals, Environmentally Stable
Military Remnants in Gaza, Palestine: A Summary
251
which confirmed a high background for weapon
related heavy metals since 2011.
Still, above the high background, differences were
found in the load of heavy. metals according to
exposures of the individuals to war related events and
their residence. Association with these exposures
persisted till 2016, when still 78% of the women
resided near the rubble generated by attacks but was
lost once the ruins were removed and pulverized in
open air by 2018, and when only 12% of women
resided near rubble. At this time the overall
background contamination did not decrease, but the
association between previous exposure and amount of
individual contamination was lost.
The unchanged high load in metals in the
population before and after removal of the war-
remnants showed that environmental “remediation
with reuse" of the war-remains, which was the only
way accessible under siege and space confinement,
may have contributed to the spread of contamination,
but hardly to its decrease.
The role of exposure to attacks and war remnants
on reproductive health was shown using more than
one approach.
First, in general, the increase in prevalence in
negative birth outcomes bridged wars. Spanning both
the war in 2009 and the couple of wars 2012 and 2014
significant increase in BD was registered; also,
prevalence in preterm births spiraled by 2016.
More in detail, the women with objectively
documented exposures to military attacks or/and war
remnants were those with higher probability to have
a BD baby or preterm delivery and had the higher load
in many heavy metals than their unexposed
concitizens. This was associated to chronic
assumption of metals, given that in all cases the
women had kept residence for about 2 years in the
same place of the attacks and of war remains thereof.
The cohort of 502 women tested for their metal
load in the immediacy of the attacks in 2014 was not
large enough to draw conclusions on the immediate
effect of birth outcome of acute exposure to these.
The prevalence of negative birth outcomes
remained in 2018-19 at the same level as in 2016,
suggesting that by then a threshold level of
"environmental factors", capable to sustain an
unabated stochastic chance of negative birth outcome,
was reached. At this time no association was found
between recall of previous exposure to attacks or
dwelling near rubble with birth outcome.
Chronic contamination of the mothers was
accompanied, to differing extent for each metal, to
passage in utero. Excess load of some metals was
found specifically associated in the hair of newborns
either with BD or preterm outcomes.
Some contaminants associated specifically with
BD or preterm were the same metals in comparable
amounts in 2011 and 2016; these were respectively
mercury and barium. and both times of testing were 2
years after a previous severe military attack.
Mercury was confirmed as inducer/co-inducer of
BD, based on its high load specifically in hair of BD
newborns, on the high load in the hair of mothers
exposed to military attacks and war remnants in
association with the higher incidence of BD progeny
in this subgroup. Mercury remained significantly high
compared to references controls throughout the years
in the population, in parallel with high frequency of
BD.
Barium was confirmed as inducer/co-inducer of
preterm births, based on its high load specifically in
hair of newborns of mothers exposed to weapons and
military remains in 2011 and 2016. Barium remained
significantly high in the population compared to
references controls throughout the years, in parallel
with higher frequency of preterm newborns.
In addition to high load of mercury for BD and of
barium for preterm in 2011 and 2016, other
contaminants were found in 2016 in newborns hair;
specifically associated with BD, was titanium which
was found in higher amounts than before in 2016;
specifically associated with preterm were arsenic and
chrome, also toxicants. Cadmium was not higher in
the hair of BD or preterm babies in 2011, while was
higher than normal in that of preterm babies in 2016.
No comparison was possible between 2011 and 2016,
for uranium and vanadium also higher in preterm in
2016, since these were not measured in 2011. Both
these last metals do not trespass quantitatively the
placenta but may have a role on the physiology of the
mother, as does barium, and influence women
capability to carry to term the pregnancy.
Recently Huang, 2021, examined in a cohort of
Bangladeshi women the load for 56 metals and
reported barium, titanium, and arsenic to be
associated with preterm birth, but did not distinguish
BD babies.
The relevance as direct effectors on BD and
preterm outcomes of the heavy metals can be
understood based on the known characteristic of their
action and the epigenetic regulation of prenatal
development by environmental factors [Perera, 2020;
Toraño, 2016
; Dabre, 2006; Granijean , 2015; Cui,
2004)].
It is not known if other heavy metals, also
chronically present in high amounts in the whole
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population in Gaza, may act in synergy with the ones
above in inducing effects on developmental health.
Thus, the use of diachronic lenses allowed to
confirm which if the various metals detected as
weapon-remnants may have a decisive role in
determining the negative reproductive outcomes,
even in compresence with other heavy metals
contaminants, but also to visualize the possible "novel
"relevance of metal effectors introduced, in kind or in
relative amounts, through weapons modernization, as
Gaza has been a "work in progress" as to the use of
weaponry for the Israeli army.
Higher prevalence of BD and preterm babies since
after 2011 translated in increase in newborn and
infant death (Maartje, 2015), with costs for families
and health care, and misery for parents and the
affected child, even more pronounced when, as in
Gaza, the possible interventions are themselves
limited by the circumstances of the siege, imposing
scarcity in economy, in medical and welfare supplies,
and limitations in professional training. These
limitations continue to endanger the chances of care
for the BD and babies born preterm that survive.
From these data, the level of increase in Gaza of
major BD and preterm babies since 2011 translated in
increase of about 1700/year additional newborn and
infant deaths.
In addition, has been reported that the further
development of children can be affected at various
stages and levels (Vänskä, 2019) by Gaza's
contaminated environment, as it happens in other
places (Alvarado-Cruz, 2018); this is an issue that
requires further studies and follow up.
Today, after another war in 2021 and the
"preventive" attacks in 2022, the contamination by
weapon remains will have increase, and the
probability of heavy metals inducing negative birth
outcomes may also have increased.
Finally, and the high load of heavy metals in the
population may be also an effector of the reported
increase in prevalence in Gaza of various non-
communicable disease, infertility, cancers, and
infective multiple antibiotic-resistant pathogens,
affecting people of all ages and sex.
The population in the world whose health might
be affected by negative long-term effects of the metal
war-remnants amounts to some hundred million of
people, and apparently war lords never take a break,
while our common environment and bases of health
continue to be devastated.
In a better world, where science could follow-up
its work smoothly, and medicine could support the
necessary development of safe care, the information
provided here would be translated in actions.
Although main molecular mechanisms were
already identified in vitro for the action of heavy
metals, which include the accumulation of excessive
reactive oxygen species, DNA damage, and over-
activation of signaling pathways, shortening of
telomeres, estrogen like action, binding to
macromolecules and interference with key structural
and enzymatic proteins, further investigations are
needed on the role of the metals “candidate” here as
inducers of BD, by testing their ability to affect cell
differentiation, communication and growth and in
model mammal's systems should be studied, in
particular eventual key stages of the development
during embryo an fetal development, the interference
of heavy metals and the effects of exposure on the
physiology of the placenta and on the proceeding of
the pregnancy; it is needed to search for molecular
biomarkers that result from exposure in vivo and
which could be used to alert of the risks before/during
human pregnancy. This work is costly and requires
structured labs and, first of all, attention to the issue.
But, in general, is possible at the state of the global
art.
Meanwhile, it is necessary that clinicians identify
substances potential “candidates for remediation” at
first among the available pharmacopeia, e.g. among
substance already widely used in pediatric age, tested
for long time of usage, for lack of side effects on
women, pregnancies, infants, and children; these
should be molecules off-patent, and widely produced
or product-able, so potentially affordable for
prevention on population scale also in countries that
have been already afflicted by wars.
At the same time, and in the better world that is
surely coming, the documented testimony of long-
term health damages by war-remnants presented here
could catch the attention of the human right advocates
and lawmakers and be considered as proof of fact of
illegitimate use of weaponry with indiscriminate ray
of action and documented consequences affecting
civilians at large and used for whatever legal and
international law implications there can be.
ACKNOWLEDGMENTS
First thanks go to the women that participated giving
their time and attention and permission to elaborate
their answers to a questionnaire and to take samples
of hair.
The list of colleagues that contributed to the
acquisition of data and their elaboration in this report
is very long; in alphabetic order: Abdallah, H., Abu
Abadi, D., Dr. Abed Y., Abu Hamad,G., Abu Mosa,
Synchronic and Diachronic Investigation of the Long-Term Effects on Reproductive Health of Heavy Metals, Environmentally Stable
Military Remnants in Gaza, Palestine: A Summary
253
T., Dr. Abu-Shaban, N., Dr. Abu-Shaban. N., Dr. Al
Baraquoni, L., Dr. Albarqouni, N.M.A., Al Dalies,
H., Al Meziny, K., Al Shawwa, R., Balousha, S., Dr.
Barbieri, M., Dr. Barbieri,M.,Dr. Diab,S.Y., El
Balawi, M., El Shawwa, R., Dr. Giani, U., Dr.
Minutolo, R., Miqdad,H., Mohammed, W.,
Myöhänen,, A., Eng.Naim, A., Dr. Parodi,
Dr.S.Perko, K., Dr. Punamäki, R.L, Dr. Qouta, S.R.,
Salah, M., Salem, E., Dr. Signoriello, S. Dr. Skaik, S.,
Dr. Vänskä, M.
Thanks for permissions and the support to 3
successive Ministers of Health in Gaza, Dr Naim B.,
Dr. Dr M.Mokallathi, peace be upon him, who
allowed to start the research when Dean of the
Medical Faculty of the Islamic University of Gaza,
Dr. Raysh Y., and gratitude to the UN Mine Action
team, to the EQA, Agency of the Environment in
Gaza, for sharing insights and information, to
UNRWA for valuable consulting, and to a number of
colleagues in Europe that supported with scientific,
pragmatical and moral advice the research all along.
The research was according to the Ethical
principles of the Helsinki convention, was approved
by the Ethical committee of the Islamic University of
Gaza and was done under permission of the Gaza
Ministry of Health.
Funds were: Italian Cooperation to P.M-, Interpal
UK to P.M, Jacobs foundation #5585within a
collaborative project with Tampere university, and all
along through the donations of benevolent individuals
or associations that support health and welfare for
Palestinians to the association NWRG, to whom goes
our gratitude.
I declare no conflict of interest of any kind.
REFERENCES
Agents Classified by the IARC Monographs, Volumes 1–
125. Available online: https://monographs.iarc.fr/
agents-classified-by-the-iarc/ (accessed on 1 April
2020).
Alvarado-Cruz, I., Alegría-Torres, J.A., Montes-Castro, N.,
Jiménez-Garza, O., Quintanilla-Vega, B. (2018)
Environmental Epigenetic Changes, as Risk Factors for
the Development of Diseases in Children: A
Systematic. Review. Ann. Glob. Health, 84, 212–224.
Amadi CN, Igweze ZN, Orisakwe OE. Heavy metals in
miscarriage and stillbirths in developing nations.
Middle East Fertility Society Journal. 2017; 22(2):91-
100. https://doi.org/10.1016/j.mefs.2017.03.003
ATSDR-Agency for Toxic Substances and Disease
Registry. The priority list of hazardous substances.
Atlanta GA): U.S. . Atlanta (GA): U.S. Department of
Health and Human Services, Public Health Service,
2011.
Baraquoni, N.A., Qouta, S.R., Vänskä, M., Diab, S.Y.,
Punamäki, R.L., Manduca, P. It Takes Time to Unravel
the Ecology of War in Gaza, Palestine: Long-Term
Changes in Maternal, Newborn and Toddlers' Heavy
Metal Loads, and Infant and Toddler Developmental
Milestones in the Aftermath of the 2014 Military
Attacks. (2020). Int J Environ Res Public Health. Sep
14;17(18):6698.
Bommarito, P..A., Martin, E., Fry, R.C. Effects of prenatal
exposure to endocrine disruptors and toxic metals on
the fetal epigenome. (2017), Epigenomics 9, 333–350.
Cheng, T..F., Choudhuri, S., Muldoon-Jacobs, K.
Epigenetic targets of some toxicologically relevant
metals: A review of the literature. (2012). J. Appl.
Toxicol. JAT, 32, 643–654.
Cui, X., Choi, S.M., Yoo, S.D., Lee, B.M. Toxicological
characteristics of endocrine-disrupting chemicals:
Developmental toxicity,carcinogenicity, and
mutagenicity. J. Toxicol. Environ. Health B Crit.
Rev. (2004), 7, 1–24.
Darbre, P.D. Metalloestrogens: An emerging class of
inorganic xenoestrogens with potential to add to the
oestrogenic burden of the human breast. J. Appl.
Toxicol. (2006) 26, 191–197.
Grandjean, P., Barouki, R., Bellinger, D.C.,Casteleyn, L.,
Chadwick, L.H., Cordier, S., Etzel, R.A., Gray, K.A.,
Ha, E.-H.; Junien, C., et al. Life-long implications of
developmental exposure to environmental stressors:
New perspectives. Endocrinology (2015) 156, 3408–
3415.
Huang, H., Wei, L.
, Chen, Zhang, R., Su, L., Rahman
,
M., Mostofa,
M.D, Qamruzzaman, Q., Zhao, Q.,
Yu,
H., Wei, Y., Christiani, D.C., Chen, F., Cord serum
elementomics profiling of 56 elements depicts risk of
preterm birth: Evidence from a prospective birth cohort
in rural Bangladesh. Environ Int. (2021) Nov;
156:106731.
van den Berg, M.M., Madi, H.H., Khader, A., Hababeh
,M.,Zeidan, W., Wesley, H., Abd El-Kader,
M., Maqadma, M.,
Seita, A., Increasing Neonatal
Mortality among Palestine Refugees in the Gaza Strip
PLoS One. (2015) Aug 4;10(8):e0135092.
doi:10.1371/journal.pone.0135092
Manduca, P., Naim, A., Signoriello, S.,.Specific association
of teratogen and toxicant metals in hair of newborns
with congenital birth defects or developmentally
premature birth in a cohort of couples with documented
parental exposure to military attacks: observational
study at Al Shifa Hospital, Gaza, Palestine. Int J
Environ Res Public Health. (2014) May 14;11(5):5208-
23.
Manduca, P. Past emerging from present recording:
reproductive health history reveals increase in
prevalence of birth defects over time, in Gaza, Palestine
LPHA (2013) Lancet oral presentation, Epublished
2014
Manduca,P., Al Baraquni, N., Albarqouni, L., Abu Abadi,
D., Abdallah, H., Abu Hamad,G., Abu Mosa, T.,
Balousha, S., Miqdad,H., Mohammed, W., Salah, M.,
El Shawwa, R. Hospital centered surveillance of births
ISWEE 2022 - International Symposium on Water, Ecology and Environment
254
in Gaza, Palestine, 2011-2017 and heavy metal
contamination of the mothers reveal long term impact
of wars. Reproductive Toxicology (2019) 86:23-32 .
Manduca, P., Al Baraquni, N., Parodi, S.Long Term Risks
to Neonatal Health from Exposure to War-9 Years
Long Survey of Reproductive Health and
Contamination by Weapon-Delivered Heavy Metals in
Gaza, Palestine. Int J Environ Res Public Health (2020)
Apr 8;17(7):2538.
Naim, A., Al Dalies, H., El Balawi, M., Salem, E., Al
Meziny, K., Al Shawwa, R., Minutolo, R., Manduca,
Synchronic and Diachronic Investigation of the Long-Term Effects on Reproductive Health of Heavy Metals, Environmentally Stable
Military Remnants in Gaza, Palestine: A Summary
255