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Published in final edited form as: Int J Environ Health Res. 2023 Jul 10;34(3):1675–1686. doi: 10.1080/09603123.2023.2234834

The Environmental Exposures in Lebanese Infants (EELI) birth cohort: an investigation into the Developmental Origins of Health and Diseases (DOHaD)

Emile Whaibeh a,b, Myriam Mrad-Nakhlé b, Norma Aouad c, Isabella Annesi-Maesano d, Nivine Abbas b, Clara Chaiban b, Jowy Abi Hanna b, Georges Abi Tayeh a,c
PMCID: PMC10976984  NIHMSID: NIHMS1953613  PMID: 37429297

Abstract

The EELI Study is a longitudinal birth cohort launched in 2021 in Lebanon to examine the long-term impact of environmental exposures on the health of prospective Lebanese mothers and infants and disease outcomes. This article delineates the adopted study design and protocols, current progress, and contextual considerations for the planning and launching of a birth cohort in a resource-limited setting. A sample of n = 135 pregnant women expecting to give birth at the Hôtel-Dieu de France University Hospital has been recruited since the study launch. Over 500 variables have been recorded for each participant, and over 1000 biological specimens have been processed and stored in a biobank for further analysis. The EELI study establishes methodological and logistic basis to explore the concept of the exposome and its implementation and to establish a toolkit of the SOPs and questionnaires that can be employed by the other countries in the Eastern Mediterranean region.

Keywords: Birth outcomes, exposure assessment, pregnancy outcomes, child health, environmental health

Introduction

The human genome has brought significant advancements in understanding of the genetic causes of various diseases (Schmutz et al. 2004). However, the role of environmental exposures in interacting with biological systems is equally crucial role, which gave rise the complementary concept of “exposome”, proposed by molecular epidemiologist Christopher P. Wild (2005). It is defined as the totality of exposures that one encounters through their life course, including the food they ingest, the air they breathe, the objects they touch, the psychological stress they endure, and the behaviors they engage in (Miller 2013). The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that the first 1000 days of life after conception, including the pregnancy and the first 2 years after birth, determine the susceptibility of individuals to non-communicable diseases (Gluckman et al. 2016). During the early stages of development, infants are at risk as environmental exposures pose can alter developmental pathways due to rapid organ growth, immature metabolism, and low body weight relative to dose of exposure (Robinson and Vrijheid 2015; Subbarao et al. 2015). As a result, many diseases that develop in adulthood may have originated in utero origin due to suboptimal intrauterine conditions, which induce adaptive fetal responses that predispose individuals to neonatal and/or chronic diseases (Gluckman et al. 2010; Fleming et al. 2018).

The Eastern Mediterranean Region (EMR) suffers from considerable environmental problems such as water scarcity and pollution, air pollution, land pollution and degradation, noise pollution, unsatisfactory waste management, and climate change (United Nations Environment Programme/Mediterranean Action Plan and Plan Bleu 2020). Environmental experts in Lebanon, a developing country in the EMR with a surface area of 10,452 km2 and an estimated population of 6.8 million, have been sounding the alarm for years about the public health problems this pollution engenders (Serhan 2016). In recent years, pregnant women, in particular, have been facing unique and unprecedented challenges: pregnancy stress, political instability, the COVID-19 pandemic, economic collapse, food insecurity, and medication shortages (Das 2021). This situation is alarming because gene-environment interactions could result in immune alterations and epigenetic changes, which could determine health and susceptibility to disease for Lebanese infants and be passed down for generations to come (Whaibeh et al. 2022).

The Environmental Exposures for Lebanese Infants (EELI) longitudinal birth cohort was launched in 2021 to examine the impact of these unique environmental exposures on the health and wellbeing of Lebanese mothers and their infants (Figure 1), especially in the development of allergic, atopic, and other chronic diseases to develop effective intervention strategies. The objectives of the EELI study are to (1) recruit over 100 pregnant women expecting to give birth at the Hôtel-Dieu de France Hospital, Beirut, (2) assess indoor and outdoor environmental exposures of participants starting from in utero life, (3) understand some of the processes leading from exposure to disease, (4) establish the methodological and logistical bases in resource-limited settings, and (5) establish a toolkit of Standard Operating Procedures (SOPs) and questionnaires that can be duplicated in other EMR countries to evaluate environmental exposures in infants. The present article introduces the planning phase, the adopted study design and protocols, current progress, and future plans for the EELI study.

Figure 1.

Figure 1.

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Environmental exposures assessed by the EELI study, timeline, and location of research activities.

Materials and methods

Study design

The EELI study is a multiphasic, broad-in-scope, pilot study. It assesses a wide range of pre-and post-natal environmental exposures at different critical time points to provide insight into the role of said exposures in the development of immunological, physiological, and microbiome patterns. Several factors are considered: familial medical history, physical and psychosocial environment, nutritional habits and patterns, past and current infections, and others. Ethical approval for the project was obtained from the ethics committee of Hôtel-Dieu de France (HDF) Hospital in Beirut.

Study area and partners

The Beirut and Mount Lebanon region was selected as the primary study area for the pilot study due to its population density, air pollution problem, heavy traffic activity, and heterogeneity in housing conditions. The EELI study is a collaborative effort between two Lebanese universities: the University of Balamand (UOB) and Saint-Joseph University (USJ) of Beirut, and it consists of a project advisory unit, a coordinating center hosted by UOB, a private obstetrics and gynecology clinic for recruitment, a university hospital where deliveries take place and biospecimens are collected at birth, and a laboratory and biorepository for the processing and storage of biological specimens.

Protocols development

The project’s advisory unit selected and defined the physical, chemical, biological, and psychosocial variables of interest, guided by the literature, to answer questions on the mechanisms linking environmental exposures to chronic illnesses in infants. Then, they defined the outcomes of interest, such as pregnancy outcomes, epigenetic modifications, and disease outcomes. Standardized questionnaires and Standard Operating Procedures (SOPs) were shared with the research team by the Health and Environment-wide Associations based on Large population Surveys (HEALS) Exposure and Health Examination Survey (EXHES) study, a longitudinal birth cohort that took place in 10 European countries, and the scientific team of the Canadian Healthy Infant Longitudinal Development (CHILD) study, which developed and tested over 400 questionnaires for more than 10 years with around 3,625 mother-child pairs. All adopted research tools were reviewed, modified to fit the context and the specifics of the EELI study, translated into Arabic, and tested. Several informal meetings were done with international researchers to inquire about logistical considerations to bear in mind before the study launch.

Recruitment

Recruitment took place in the second and third trimesters. Participants were recruited at their routine antenatal obstetric ultrasound visits at the partner private clinic. The inclusion criteria included: being Lebanese, being 18 years and above, living in the Beirut and Mount Lebanon region for more than 5 years, being able to read, write, and speak Arabic, English, or French, and planning to give birth at the participating hospital, willing to provide informed consent and biological specimen for the EELI study. On the other hand, individuals who have at least 1 of the following criteria were excluded from the study: expecting to move outside of the Beirut or Mount Lebanon region or the country within less than 4 months, spending less than 80% of their nights in their indexed house in the Beirut or Mount Lebanon region, giving birth to infants before 35 weeks of gestation or with major congenital abnormalities or respiratory distress syndrome.

Data collection and exposure assessment

General demographic, environmental, health, and socio-economic questionnaires were completed by the participants. Exposure to physical, chemical, biological, nutritional, and socio-economic factors/variables was considered. Biospecimens were collected during the prenatal phase and at birth. Information regarding the first two trimesters was recorded by a trained midwife at the gynecologist’s clinic. Delivery and birth data were obtained from hospital records after taking the approval of both the hospital and the participants. As for early-life exposures data, they were collected via:

  1. Biological samples were obtained from the mothers and their infants: parental venous blood, cord blood, meconium, and colostrum samples.

  2. Clinical Assessments related to fetal development

  3. Questionnaires covering the following domains: family history, prenatal maternal health conditions, socio-economic variables, nutrition, mental health, etc.

  4. Questionnaires covering exposures in the home environment, including second-hand smoke, cleaning and chemical products, personal and childcare products, pets, traffic-related pollution (distance from main roads), ventilation and heating systems, and indoor air pollutants measurement.

After birth, house visits are conducted at 1 year and 3 years of recruitment to collect biological specimen and to complete questionnaires about the health and development of the child as well as the health of the mother and any modifications in the home environment (Figure 1).

Data management plan

Due to the COVID-19 pandemic, the EELI study had to rely on digital solutions when it comes to data collection and management. All questionnaires are in Arabic and completed online as computer-assisted telephone interviews because we did not want to put pregnant women and, later, new mothers at risk. When participants stated a preference to self-administer the questionnaires for scheduling or privacy issues, they were also given the option to do so. All biological specimens have been collected following specific SOPs to process and store them. Clear labeling and coding of each specimen were set and implemented with all involved researchers being sufficiently trained to follow the protocols. All questionnaires have specific codes to replace the participant’s name. No identifiable data was shared except among the primary investigators. All data collected from this research project was kept confidential and used only for scientific reasons. Collected data is saved on the cloud by an account with two-factor authentication. Only 2 individuals have access to the account. The password is stored in a digital key vault, not saved anywhere as plain text, and changed every six months. All saved data is encrypted and backed up on a hard drive, and only the primary investigators have access to the device, which rarely gets connected to the internet.

Ethical considerations and informed consent

Throughout the study, the researchers ensured that the internationally recognized ethical principles for research involving human subjects were respected. All the members of the research team had signed confidentiality agreements upon joining. All participants were informed fully about the research before they decided to participate or not. The information sheet included explanations about the basic elements of this research including its purpose, type of research intervention, participant selection, voluntary participation, procedures, duration, risks, benefits, reimbursements, confidentiality, sharing the results, right to refuse or withdraw, IRB approval, and who to contact for more information. All participants voluntarily participated, signed, and gave their written consent before filling out the surveys or doing their medical tests. A copy of the full Informed Consent Form was given to the participants.

Results

Descriptive results of phase I of the EELI cohort

Mothers’ characteristics

To date, the EELI birth cohort study has recruited 135 pregnant women since its launch in 2021, and the data collection and analysis are still ongoing. The mean age of the participants (N = 128) is 33.37 ± 4.21 at enrollment, with the youngest being 24 and the oldest 44. At year 1, the study retention rate is 92.2%. Table 1 presents the demographic characteristics of the study participants. Sample sizes differ for some variables due to differences in missing values and survey completion rate. The majority of the participants (81.6%) hold a university degree, with 35.2% holding a bachelor’s degree, 43.2% holding a master’s degree, and 3.2% holding a doctoral degree. Only one-third (29.6%) of the participants were unemployed while the rest were either self-employed (16%) or held part-time (4%) or full-time positions (50.4%).

Table 1.

Baseline Characteristics of the EELI Study’s recruited mothers, their infants and their home environments*

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Maternal Mean Age in years (N = 128) 33.3 ±4.2 Sex (N = 141) Years spent in residence (N = 76) 5.7 ± 7.6 years
Highest Educational Attainment (N = 125) Boys 57/141 (40.4%) When was your house built? (N = 76)
Highschool or less 23 (18.4%) Girls 72/141 (51.1%) Before 1990 15/76 (19.7%)
Bachelor’s Degree 44 (35.2%) Undetermined at the time of call 12/141 (8.5%) 1990–1999 4/76 (5.3%)
Master’s Degree 54 (43.2%) Fetal Biometry in the 3rd Trimester (N = 71) 2000–2009 9/76 (11.8%)
Doctorate Degree 4 (3.2%) Biparietal Diameter (in mm) 6.5 ± 0.5 2010 and after 38/76 (50%)
Employment Status (N = 125) Head circumference (in mm) 23.4 ± 3 I don’t know 10/76 (13.1%)
Unemployed 37 (29.6%) Abdominal Circumference (in mm) 22.1 ±1.7 House Surface Area (N = 76)
Full-time employed 63 (50.4%) Femur Length (in mm) 4.7 ± 0.4 50–100 m2 5/76 (6.6%)
Part-time employed 5 (4%) Birth weight 101–150 m2 23/76 (30.2%)
Self-employed 20 (16%) Less than 2500 g 9/77 (11.7%) 151–200 m2 31/76 (40.8%)
MacArthur Subjective Social Status Score (N = 125) 2500 g-4200 g 68/77 (88.3%) 201–250 m2 6/76 (7.9%)
Within community 6.5 ± 1.4 Apgar Score at 1 min More than 250 m2 11/76 (14.5%)
Nationally 5.9 ±2 Less than 7 4/77 (5.2%) Rented or owned? (N = 125)
Preexisting Health Conditions 7 and above 73/77 (94.8%) Rented 21/125 (16.8%)
Any reported breathing problems 29/109 (26.6%) Average Score (N = 77) 8.5 ±1.12 Owned 103/125 (82.4%)
Reported Asthma 6/109 (5.5%) Apgar Score at 5 min Rather not say 1/125 (0.8%)
Any reported allergy 86/109 (78.8%) 7 and above 100% Type of house (n = 76)
Ever smoked in the past 48/109 (44%) Average Score (N = 77) 9.4 ±0.6 Independent house single family 6/76 (7.9%)
Mean Years spent smoking (N = 48) 12.8 ±5.2 Reason to Use Incubator Independent house more than 1 household 2/76 (2.6%)
Smoking during preg. (N = 48) 8/48 (16.6%) Jaundice 1/74 (1.3%) Apartment 4 story building or less 24/76 (31.6%)
Parity Risk of Infection 2/74 (2.7%) Apartment in more than 4 stories building 44/76 (57.9%)
Nulliparous 69/117 (58.9%) Family History Parking
Primiparous 39/117 (33.4%) Asthma 17/71 (23.9%) Building has underground parking 48/76 (63.2%)
2 or more 9/117 (7.6%) Allergic Rash 22/109 (20%) Building has open air parking 21/76 (27.6%)
Mean Gestational Age (N = 74) 38 w 4 d ±8 d Eczema/Atopic Dermatitis 24/109 (22%) Building has no parking 7/76 (9.2%)
Pregnancy Term (N = 74) Urticaria/Hives 13/109 (11.9%) Parking Capacity (N = 67)
Less than 37 weeks 2 (3%) Allergic Rhinitis 41/109 (37.6%)  1–10 34/67 (50.7%)
37 weeks and above 72 (97%) Arthritis 18/109 (16.5%)  11–20 20/67 (29.8%)
Mode of Delivery (N = 74) Thyroid disease 26/70 (37.1%)  More than 20 13/67 (19.4%)
Vaginal Birth 32 (48.6%) Kidney disease 16/109 (14.7%) Pets (N = 65)
Caesarean Section 38 (51.4%) Irritable bowel syndrome 13/109 (11.9%) No pets 43/65 (66.1%)
Pregnancy Complications (N = 74) Heart disease 49/109 (45%) Cats 11/65 (16.9%)
Fetal Arrhythmia 11/74 (14.8%) High blood pressure 79/109 (72.5%) Dogs 9/65 (13.8%)
Meconium-stained amniotic fluid 8/74 (10.8%) Diabetes 65/109 (59.6%) Birds 2/65 (3%)
Labor dystocia/protracted labor 5/74 (6.7%) High blood cholesterol 69/109 (63.3%) Fish 2/65 (3%)
Vaginal delivery failure after induction 4/74 (5.4%) Anemia 31/109 (28.4%) Humidity (N = 76)
Stagnation of dilation during labor 3/74 (4%) Osteoporosis 28/109 (25.7%) Reported Moldy Smell 24/76 (31.6%)
Hyperalgesia 2/74 (2.7%) Cancer 54/109 (49.5%) Reported Visible Signs of Mold 32/76 (42.1%)
Placenta previa with hemorrhage 1/74 (1.3%) Reported Condensation on windows during moderate weather 26/76 (31.6%)
Postpartum Maternal Complications Reported Condensation on bathroom mirror hours after taking a shower 13/76 (17.1%)
Minimal hemorrhage 9/74 (12.16%) Reported Water Leakage 28/76 (36.8%)
Severe Hemorrhage 1/74 (1.3%) Indoor Air Quality
Fever 2/74 (2.7%) Reported Visible Traffic-related Smoke 13/76 (17.1%)
Acute Hemorrhoidal crisis 2/74 (2.7%) Can smell Traffic-related smoke 14/76 (18.4%)
Uterine Atony 1/74 (1.3%) Reported living with smokers 32/87 (36.7%)
No complications 59/74 (79.7%) Reported indoor smoking 29/86 (33.7%)
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*

Data are presented as n (%) or as n/N (%) with N being the total sample available or that variable. Sample sizes differ for some characteristics due to differences in missing values and survey completion rate.

For pre-existing health conditions, out of 109 participants, 86 (78.8%) reported never having had any allergies; 29 (26.6%) did not report any breathing problems in the past, and only 6 (5.5%) participants reported having asthma. Forty-eight participants (44%) never smoked in the past. Among women who have ever smoked in the past (n = 48), the mean years spent smoking was 12.8 ± 5.2 with 16.6% (N = 8) having continued to smoke during their pregnancy.

Regarding parity, 39 (33.4%) of the participants were nulliparous, 69 (58.9%) were primiparous, and 9 (7.6%) were pluriparous. The mean gestational age for the 74 mothers that gave birth by the time of conducting this analysis was 38 weeks and 4 days ±8 days. Only 3% of the participants had a premature pregnancy of less than 37 weeks. For the mode of delivery, half of the participants (51.4%) had a cesarean section while the other half (48.6%) had a vaginal delivery. When it comes to pregnancy complications, out of 74 participants, 11 (14.8%) had fetal arrhythmia, 8 (10.8%) had meconium-stained amniotic fluid, 5 (6.7%) had labor dystocia or protracted labor, 4 (5.4%) failed to have vaginal delivery failure after induction, 3 (4%) had stagnation of dilation during labor, 2 (2.7%) had hyperalgesia and 1 (1.3%) had placenta previa with hemorrhage. For postpartum maternal complications, the majority of participants (79.7%) experienced no complications; 9 (12.16%) had minimal hemorrhage; 2 (2.7%) had a fever and acute hemorrhoidal crisis and only 1 (1.3%) experienced severe hemorrhage and uterine atony.

Infants’ characteristics

To date, the total number of infants enrolled in the EELI study is 141, consisting of 56 (43%) boys, 65 (50%) girls, and 8 (7%) of undetermined sex. None of the participants in the cohort had two separate pregnancy and that the infants outnumber the mothers due to twin pregnancies. As for the fetal biometry in the 3rd trimester (n = 71), the mean average is 6.5 ± 0.5 for biparietal diameter (in mm), 23.4 ± 3 for head circumference (in mm), 22.1 ± 1.7 for abdominal circumference (in mm) and 4.7 ± 0.4 for femur length (in mm). Out of 77 born infants, only 9 (11.7%) weighed less than 2500 g at birth. Similarly, only 4 (5.2%) scored less than 7 on their 1-minute Apgar score and none of the children had an Apgar of less than 7 at 5 minutes. Only 3 out of the 74 born infants needed an incubator after birth, with one needing it because of jaundice and 2 because of the risk of infection.

The majority of infants (72.5%) have a family history of high blood pressure. Most have a family history of high blood cholesterol (63.3%) and diabetes (59.6%) diabetes. 37.1% have a history of thyroid disease, 25.7% have a history of osteoporosis, and 11.9% of irritable bowel diseases. Regarding allergic diseases, 37.6% have a family history of allergic rhinitis, 23.9% have a family history of asthma, 22% have a history of atopic dermatitis, 20% have allergic rashes, and 11.9% have hives. Approximately half of the participants (49.5%) have family members who were previously diagnosed with cancer.

Home environment characteristics

At the time of this analysis, 76 participants completed the house environment questionnaire. The geographic distribution of the participants is presented in Figure 2. The average time of residency is 5.7 ± 7.6 years, with half of the participants (50%) residing in relatively new homes built since 2010. Most of the participants had homes with a surface area between 151–200 m2 (40.8%) and 101–150 m2 (30.2%). The majority of the participants live in apartment buildings (89.5%) and own their homes (82.4%). The majority of the residences have parking, with 63.2% of the participants living in buildings with underground parking lots.

Figure 2.

Figure 2.

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Map of the main place of residence of the EELI study participants (N = 127), segregated by Districts or Kaza. The area is dark blue represents the Beirut and Mount Lebanon region.

Regarding indoor air quality, 17% of participants reported having visible traffic-related smoke in their homes and 18.4% reported smelling it. Two-thirds of the participants (66.1%) reported not having any pets indoors, while 16.9% reported having cats and 13.8% reported having dogs. Regarding indoor humidity, 31.6% (n = 24) reported a moldy smell indoors; 42.1% (n = 32) have spotted visible signs of mold in their houses; 31.6% have seen condensation on windows during moderate weather, 17.1% have noticed condensation on the bathroom mirrors hours after taking a shower, and 36.8% reported water leakage inside their houses.

Discussion

One year since its launch, the EELI longitudinal birth cohort pilot study was successful in meeting its first objective of recruiting over 100 mother-infant pairs, with a total of N = 135 women and their 141 infants enrolled in the study, and managed to maintain a high retention rate of 92.2% for year 1. Birth cohort studies are challenging and require time, resources, and continuous engagement with participants to mitigate loss-of-follow-up and withdrawals. Low- and middle-income countries face additional challenges due to limited funding, delays in analysis and result sharing, political instability, and social stressors that might affect participant engagement.

The EELI study succeeded in conducting a preliminary assessment of the indoor and outdoor prenatal exposures of the enrolled participants who completed so far seven unique questionnaires covering the following domains: socio-demographic characteristics, maternal personal health history, infant’s family history, current health behavior and lifestyle, nutrition, maternal mental health, and psychosocial wellbeing. In addition to epidemiological data, biological specimens were collected both prenatally and at birth. Biospecimens include prenatal venous blood samples, cord blood samples, meconium samples, and colostrum samples. After 1 year, the EELI study has in its biorepository a total of 1,638 aliquots, all collected, processed, and stored following pre-defined standardized SOPs based on similar international birth cohort studies. While setting up a biorepository of human specimens is generally quite challenging, it is even more complicated in low- and middle-income countries because it is a labor-intensive task that requires good infrastructure, affordable and reliable transportation, reliable electricity and technology, and a large amount of often expensive materials and consumable. The launching of the EELI study launch coincided with the COVID-19 lockdown measures and mobility restrictions, a fuel crisis that made transportation more difficult and costly and made power cuts a more common occurrence, a deterioration of the Lebanese currency paired with a global disruption in production chains, which delayed and complicated the acquisition of all the necessary equipment and materials. However, the aspect that was most critical was ensuring that our laboratories are receiving a constant and reliable supply of electricity to avoid losing any samples from the participants. To mitigate this risk, duplicates of each type of biospecimen for each participant were made and stored in two different locations: the UOB research laboratory and Hotel-Dieu de France University Hospital.

Regarding the characteristics of the EELI study cohort, the majority of the enrolled women had a high level of education, were employed during their pregnancy, had full-term pregnancies, and had previously experienced at least one successful birth prior to their enrollment. It was also discovered that 16.6% of the women in our cohort continued to smoke during pregnancy. This percentage is slightly lower than a prevalence determined by a cross-sectional study by Chaaya et al. (2003), which found smoking prevalence among pregnancy women in Lebanon at 20%. A meta-analysis by Philips et al. (2020) examining 28 births cohorts from Europe and North America revealed a wide range of smoking rates during pregnancy, varying between 5.5% and 26.8%, placing Lebanon in the upper ranges in this regard. Concerning the mode of delivery, half of the participants underwent a Cesarean section, which aligns with the findings of another study conducted at HDF that assessed the prevalence of Cesarean section births and found it to be 56.8% (Abdallah et al. 2022). This rate is higher compared to the majority of European countries, where Cesarean section rates range from 14.8 to 52.2%, with only Cyprus (52.2%) having a similar rate to Lebanon (Macfarlane et al. 2016). Additionally, common pregnancy complications observed in our cohort included fetal arrhythmia (14.8%) and meconium-stained amniotic fluid (10.8%). The prevalence of the latter falls within the global range of 7 to 22% (Addisu et al. 2018); however, fetal arrhythmia appears to be more pronounced compared to the general prevalence of 1 to 3% (Aggarwal et al. 2009). One possible hypothesis worth exploring is the potential impact of nicotine exposure during pregnancy, as nicotine has been shown to increase cardiovascular risks in offspring, including the risk of fetal arrhythmia (Tairy et al. 2019).

Collected biospecimens will be used for biomarker testing to detect critical exposures and early effects or disease susceptibility, particularly to asthma and allergic diseases. Personal-level exposure assessment is important in contexts where continuous pollution monitoring and environmental surveillance are not sufficiently implemented by governmental entities. Without exposure data, it is difficult to determine which environmental exposures are most prevalent and critical to the development and well-being. This complicates the effective development of intervention strategies, such as awareness campaigns or advocacy to ban, limit the use or replace certain pollutants (Mahesh 2019). Research has linked environmental conditions and lifestyle factors, including diet, health beliefs, and health-seeking behaviors are associated with allergy risk and disease reporting among populations. Moreover, environmental chemical contamination is a widely acknowledged problem worldwide and constitutes a major threat to intergenerational equity and ecosystem sustainability (Arnold et al. 2014; Brack et al. 2017). Low concentrations of these compounds are not expected to produce acute effects, but low-level chronic exposures may trigger effects at the endocrine, reproductive, or developmental level. The Canadian Healthy Infant Longitudinal Development (CHILD) is a very important example of how birth cohort studies can help elucidate the interactions between the environment and genetics in the development of asthma and allergy and potentially other common chronic diseases (Takaro et al. 2015).

In the EMR, there have been previous birth cohorts that aimed to study DOHaD before. For instance, in 2015, the Mother and Infant Nutritional Assessment (MINA) cohort study was conducted in Qatar and Lebanon to investigate the association of nutrition imbalances early in life with birth outcomes, growth patterns, as well as early determinants of non-communicable diseases. While they examined the effects of maternal and early child nutrition and lifestyle characteristics on birth outcomes and growth patterns, they did not take into consideration the environmental exposures before and after birth and their effects on the growth and development of children (Naja et al. 2016). Similarly, in 2016, the Prospective Epidemiological Research Studies in Iran (PERSIAN) birth cohort study assessed the impact of socio-environmental, psychosocial, and genetic factors on pregnancy outcomes and early- and late-onset NCDs (Eghtesad et al. 2017). However, both Iran and Qatar are considered resource-rich countries and their methodologies and protocols are not easily replicable in other resource-limited settings. Furthermore, tools developed in Farsi cannot be used in the rest of the EMR, as the majority of country use Arabic as their official language. The EELI study contributes to the field of DOHaD investigation in the EMR by setting the logistic and methodological basis for resource-limited settings and creating SOPS and tested and validated questionnaires in Arabic that can be replicated in other Arabic-speaking countries. Moreover, alterations in gene expression due to environmental exposure are predominantly associated with alteration of epigenetics signature, such as DNA methylation or histone modifications (Feil and Fraga 2012; Whaibeh et al. 2022). The possible impact of the environment on epigenetic regulation – particularly differently methylated genes associated with the atopy risk – is of particular interest to the researchers of the EELI study. Finally, the EELI study includes nested cohort studies focused on the influence of maternal diet on infant gut microbiome and the influence of the COVID-19 pandemic, economic crisis, and indoor environmental exposures on maternal mental health are conducted on sub-populations of the study.

To the best of our knowledge, the EELI study is the first environmental health-focused birth cohort study in Lebanon and one of the few longitudinal birth cohort studies in the region. The EELI study follows a cohort of women who were pregnant and gave birth during turbulent times in the country’s history. The cohort also follows infants who were conceived and born and who spent their early childhood in lockdown, under unusual circumstances, hence the uniqueness and the non-repeatability of some of these environmental and social exposures. This pilot study allows the researchers to develop much-needed SOPs and questionnaires in Arabic and is and test the feasibility of several sub-studies to lay the ground for future multi-centric and larger studies in scale and scope. By shedding light on unique environmental and social exposures faced by Lebanese mothers and infants, the findings that the EELI study will help inform evidence-based medical practice, interventions, and policies.

Acknowledgements

We are grateful to all the women who enrolled in our study and who are contributing to the production of the wealth of knowledge that the EELI study is able to generate for Lebanon and the region. We would also like to extend our acknowledgment to the entire EELI study team and those who contributed to the success of the study in the first year of its launch.

Funding

The research was made possible by an intramural fund from the University of Balamand. The work of Dr. Myriam Mrad is partially funded by an NIH Fogarty International Center grant (Reference number: [1U01TW012237-01].

Footnotes

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, MM. The data are not publicly available due to containing information that could compromise the privacy of the research participants.

References

  1. Abdallah W, Abi Tayeh G, Cortbaoui E, Nassar M, Yaghi N, Abdelkhalek Y, Kesrouani A, Finan R, Mansour F, Attieh E, et al. 2022. Cesarean section rates in a tertiary referral hospital in Beirut from 2018 to 2020: Our experience using the Robson classification. Int J Gynecol Obstet. 156(2):298–303. doi: 10.1002/ijgo.13653. [DOI] [PubMed] [Google Scholar]
  2. Addisu D, Asres A, Gedefaw G, Asmer S. 2018. Prevalence of meconium stained amniotic fluid and its associated factors among women who gave birth at term in Felege Hiwot comprehensive specialized referral hospital, North West Ethiopia: a facility based cross-sectional study. BMC Pregnancy Childbirth. 18(1):1–7. doi: 10.1186/s12884-018-2056-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aggarwal S, Czaplicki S, Chintala K. 2009. Hemodynamic effect of fetal supraventricular tachycardia on the unaffected twin. Prenat Diagn. 29(3):292–293. doi: 10.1002/pd.2136. [DOI] [PubMed] [Google Scholar]
  4. Arnold KE, Brown AR, Ankley GT, Sumpter JP. 2014. Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems. Phil Trans R Soc B. 369(1656):20130569. doi: 10.1098/rstb.2013.0569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brack W, Dulio V, Ågerstrand M, Allan I, Altenburger R, Brinkmann M, Bunke D, Burgess RM, Cousins I, Escher BI. 2017. Towards the review of the European Union water framework directive: recommendations for more efficient assessment and management of chemical contamination in European surface water resources. Sci Total Environ. 576:720–737. doi: 10.1016/j.scitotenv.2016.10.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chaaya M, Awwad J, Campbell OM, Sibai A, Kaddour A. 2003. Demographic and psychosocial profile of smoking among pregnant women in Lebanon: public health implications. Matern Child Health J. 7:179–186. doi: 10.1023/A:1025136421230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Das M 2021. Lebanon faces critical shortage of drugs. Lancet Oncol. 22(8):1063. doi: 10.1016/S1470-2045(21)00396-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eghtesad S, Mohammadi Z, Shayanrad A, Faramarzi E, Joukar F, Hamzeh B, Farjam M, Sakhvidi MJZ, Miri-Monjar M, Moosazadeh M. 2017. The PERSIAN cohort: providing the evidence needed for healthcare reform. Arch Iran Med. 20(11):691–695. [PubMed] [Google Scholar]
  9. Feil R, Fraga MF. 2012. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 13 (2):97–109. doi: 10.1038/nrg3142. [DOI] [PubMed] [Google Scholar]
  10. Fleming TP, Watkins AJ, Velazquez MA, Mathers JC, Prentice AM, Stephenson J, Barker M, Saffery R, Yajnik CS, Eckert JJ. 2018. Origins of lifetime health around the time of conception: causes and consequences. Lancet. 391 (10132):1842–1852. doi: 10.1016/S0140-6736(18)30312-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gluckman PD, Buklijas T, Hanson MA. 2016. The developmental origins of health and disease (DOHaD) concept: past, present, and future. The epigenome and developmental origins of health and disease place unknown. Elsevier. p. 1–15. doi: 10.1016/B978-0-12-801383-0.00001-3. [DOI] [Google Scholar]
  12. Gluckman PD, Hanson MA, Buklijas T. 2010. A conceptual framework for the developmental origins of health and disease. J Dev Orig Health Dis. 1(1):6–18. doi: 10.1017/S2040174409990171. [DOI] [PubMed] [Google Scholar]
  13. MacFarlane AJ, Blondel B, Mohangoo AD, Cuttini M, Nijhuis J, Novak Z, Ólafsdóttir HS, Zeitlin J, Euro‐Peristat Scientific Committee. 2016. Wide differences in mode of delivery within Europe: risk‐stratified analyses of aggregated routine data from the Euro‐Peristat study. BJOG: Int J Obstet Gynaecol. 123(4):559–568. doi: 10.1111/1471-0528.13284. [DOI] [PubMed] [Google Scholar]
  14. Mahesh PA. 2019. Implementing precision medicine in best practices of chronic airway diseases. Indian J Med Res. 149(6):802. doi: 10.4103/ijmr.IJMR_608_19. [DOI] [Google Scholar]
  15. Miller GW. 2013. The exposome: a primer, place unknown. Elsevier. doi: 10.1016/B978-0-12-417217-3.00001-X. [DOI] [Google Scholar]
  16. Naja F, Nasreddine L, Al Thani AA, Yunis K, Clinton M, Nassar A, Farhat Jarrar S, Moghames P, Ghazeeri G, Rahman S. 2016. Study protocol: mother and infant nutritional assessment (MINA) cohort study in Qatar and Lebanon. BMC Pregnancy Childbirth. 16(1):1–11. doi: 10.1186/s12884-016-0864-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Philips EM, Santos S, Trasande L, Aurrekoetxea JJ, Barros H, von Berg A, Bergström A, Bird PK, Brescianini S, Ní Chaoimh C, et al. 2020. Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births. PLoS Med. 17(8):e1003182. doi: 10.1371/journal.pmed.1003182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Robinson O, Vrijheid M. 2015. The pregnancy exposome. Curr Envir Health Rpt. 2(2):204–213. doi: 10.1007/s40572-015-0043-2. [DOI] [PubMed] [Google Scholar]
  19. Schmutz J, Wheeler J, Grimwood J, Dickson M, Yang J, Caoile C, Bajorek E, Black S, Chan YM, Denys M. 2004. Quality assessment of the human genome sequence. Nature. 429(6990):365–368. doi: 10.1038/nature02390. [DOI] [PubMed] [Google Scholar]
  20. Serhan R 2016. Lebanon suffers pollution by land, sea and air citzens’ average age down by 25%. Lebanese: National News Agency; [Internet]. [accessed 2023 Mar 16]. https://www.nna-leb.gov.lb/en/hotreports/224167/lebanon-suffers-pollution-by-land-sea-and-air-citz [Google Scholar]
  21. Subbarao P, Anand SS, Becker AB, Befus AD, Brauer M, Brook JR, Denburg JA, HayGlass KT, Kobor MS, Kollmann TR. 2015. The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma. Thorax. 70(10):998–1000. doi: 10.1136/thoraxjnl-2015-207246. [DOI] [PubMed] [Google Scholar]
  22. Tairy D, Gluck O, Tal O, Bar J, Katz N, Hiaev Z, Kovo M, Weiner E. 2019. Amniotic fluid transitioning from clear to meconium stained during labor—prevalence and association with adverse maternal and neonatal outcomes. J Perinatol. 39(10):1349–1355. doi: 10.1038/s41372-019-0436-4. [DOI] [PubMed] [Google Scholar]
  23. Takaro TK, Scott JA, Allen RW, Anand SS, Becker AB, Befus AD, Brauer M, Duncan J, Lefebvre DL, Lou W. 2015. The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: assessment of environmental exposures. J Expo Sci Environ Epidemiol. 25(6):580–592. doi: 10.1038/jes.2015.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. United Nations Environment Programme/Mediterranean Action Plan and Plan Bleu. 2020. The 2020 edition of the State of the Environment and Development in the Mediterranean (SoED) [Internet]. Nairobi; [accessed 2023 Mar 16]. https://planbleu.org/wp-content/uploads/2021/04/SoEDfull-report.pdf [Google Scholar]
  25. Whaibeh E, Tayeh GA, Farah W, Abboud M, Awar SE, Affara HL, Chalhoub E, Mrad M. 2022. Air pollution and perinatal health in the eastern Mediterranean region: challenges, limitations, and the potential of epigenetics. Curr Envir Health Rpt. 9(1):1–10. doi: 10.1007/s40572-022-00337-9. [DOI] [PubMed] [Google Scholar]
  26. Wild CP. 2005. Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev. 14(8):1847–1850. doi: 10.1158/1055-9965.EPI-05-0456. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author, MM. The data are not publicly available due to containing information that could compromise the privacy of the research participants.

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