Maternal risk Factors of childhood cancer in Libya: an exploratory study

Introduction

Childhood cancers have been rising over the last few decades worldwide. Leukemia and brain tumors are among the most common childhood cancers [1]. There are several risk factors related to malignancy in childhood,which can be genetic, environmental, or related to prenatal exposures.Certain genetic conditions, such as Li-Fraumeni syndrome, neurofibromatosis, and Down syndrome, significantly increase the risk of developing childhood cancers, particularly leukemia and brain tumors.Some cancers, like retinoblastoma, are linked to inherited genetic mutations that predispose children to cancer [2].

Many of the following maternal factors have been reported to increase the risk for childhood cancers.Maternal age, studies have shown that children born to younger mothers may have a higher incidence of certain cancers [3].Maternal obesity and high body mass index(BMI) have been suggested as a potential risk factor for childhood cancer, although findings are mixed and further research is needed[4]. Previousmiscarriages and a history of miscarriages may be linked to an increased risk of childhood cancer in subsequent pregnancies [5]. Maternal comorbidities [6], such as maternal hypothyroidism has been linked to an elevated risk of childhood lymphomas, particularly acute lymphoblastic leukemia [7].Additionally, Maternal diabetes, particularly type I diabetes, has been associated with an increased risk of certain childhood cancers, such as glioma and hepatoblastoma [8]. Maternal anemia, research indicated that maternal anemia during pregnancy is associated with an increased risk of several childhood cancers, including neuroblastoma and acute lymphoblastic leukemia. The study suggested that screening for anemia and vitamin supplementation could be beneficial strategies [9]. Furthermore, nutritional Factors, a maternal diet during pregnancy play a role in childhood cancer risk. Regular consumption of fruits and folic acid supplementation has been suggested to offer protective effects against acute leukemia. Conversely, high caffeine intake during pregnancy may be linked to increased cancer risk [10].Maternal occupationis also considered, a study found statistically significant associations between childhood leukemia and maternal occupation, particularly for mothers working in agriculture who were exposed to pesticides during pregnancy. This exposure was linked to an increased risk of leukemia in children [11].

Moreover, perinatal risk factors are related to childhood cancer, including, low Apgar Score at 5 minutes after birth has been associated with an increased risk of childhood cancer. This may reflect complications during delivery that could impact long-term health [12]. More importantly, delivery method, children delivered by cesarean section have shown some associations with an increased risk of certain childhood cancers, although the reasons for this are not entirely clear [13].Birth weight, such as preterm birth and low birth weight have been investigated for their potential links to childhood cancer, with some studies indicating associations [14,15].

While maternal and perinatal factors are significant, environmental exposures also play a role in childhood cancer risk. Exposure to parental smoking, especially paternal pre-conceptional and during pregnancy smoking, has been suggested as a potential risk factor for childhood cancers [16]. Moreover, Traffic-related air pollution exposure during pregnancy and early life has been linked to childhood cancers [17].  Living near air-polluting industries or nuclear power plants may increase the risk of certain childhood cancers[18]. Further, infections with certain viruses, such as Epstein-Barr virus (EBV) and HIV, are associated with an increased risk of specific childhood cancers, including lymphomas [19]. The social dimension of childhood cancer is also considered in terms of family structure and parentaldivorce. Offspring of divorced parents have been found to have increased risks of certain cancers like upper aerodigestive tract, esophageal, anal, pancreatic, lung, and cervical cancers compared to offspring of stably married parents [20].

Overall,many of these risk factors can increase the likelihood of childhood cancer, however, the evidence is still conflicting [21].It is important to note that having one or more risk factors does not guarantee that a child will develop cancer. However, the findings of these studies emphasize the importance of considering maternal health conditions, environmental exposures, and lifestyle factors in understanding and potentially mitigating the risk of childhood cancer development.

In Libya, childhood cancer has been a public health concern. Causing a substantial burden on the families and health care system.  Many efforts in the society to investigate the influencing risk factors. The etiology of the increased trends of malignanciesremains unexplained. Limited studies on childhood cancer risk factors in Libya. This study explores some maternal risk factors for childhood cancer in Benghazi.

Methods

A cross-sectional survey was conducted on a convenient sample of mothers admitted with their children at the Benghazi pediatric hospital in April 2024. Data was collected by interviewing mothers to answer the administered questionnaire on maternal risk factors of childhood cancer. The participation was voluntary and verbal personal consent was taken from the mothers, all data was kept confidential and anonymized. Data entered and analyzed by SPSS program version 22. A descriptive statistical analysis was performed. Results were presented in tables and figures.

Results:

A total of 21 mothers voluntarily participated in answering the administered questionnaire. 33.3% of mothers in the sample were between 25 and 29 years old at birth, the same percentage was reported for mothers in the age category 30 and more. While the percentage of mothers who were 24 years old or younger was relatively lower. Mean age of mothers as shown in

Discussion

As mentioned, various maternal risk factors have been identified as significantly associated with the development of childhood cancers.Understanding the maternal risk factors is important for developing effective prevention and management strategies. In our study conducted at Benghazi Hospital, we explored some maternal factors reported in the pieces of literature as being relatedto the incidence of pediatric cancer. Including maternal Age, mode of delivery, and exposure of mothers to certain factors that contribute to cancer in children during pregnancy.

In light of existing literature, the findings still conflicting regarding the maternal risk factors of cancer in children including maternal age at delivery, maternal anemia, history of miscarriage^, maternal overweight, and smoking^.With consideration to the difference in study design in comparison to previous literature, our observational exploratory study indicates the use of dyed hair during pregnancy as a suspected factor was observed among the majority of mothers, which is considered to be among the dangerous materials on the fetus, especially in the first trimester, and associated with risk of leukemia and retinoblastoma [22],[23].  Generally, maternal hair dye use is associated with an elevated risk of various fetus outcomes [24],[25]. Maternal hair dyeing-induced childhood tumors by using hair dyes contain Endocrine-disrupting chemicals [26].However, evidence still conflicting regarding the risk of cancer, a recent study found no association between risk for childhood brain tumors and the use of hair dyes during pregnancy [27].This implies careful interpterion of results regarding subtypes of childhood cancer.

While several risk factors have been identified globally that could be related childhood cancer, specific studies on maternal risk factors for childhood cancer in Libya are not extensively documented.A previous study in the west of Libya has looked at different risk factors of leukemia suggesting that maternal age (<35 years) has a slight effect on increasing the risk of leukemia [28].Likewise, other studies found specific cancers like acute lymphoblastic leukemia and retinoblastoma also show increased odds with advancing maternal age [29]. In contrast, our results found a similar number of mothers aged 25to30 years and 40 years. Although our findings are not conclusive but were in line with other studies found younger maternal age at delivery is associated with an increased risk of childhood cancer [3]. However, the relationship is complex and controversial, and need further investigations and adjustments to specific cancers and other maternal factors.

Maternal exposure to lead in Libya can pose significant health risks to children, including potential links to cancer. A cross sectional study have shown moderate blood lead levels among pregnant women in Tripoli and Ghadames regions. This exposure can be attributed to various sources, including lead-based paints, contaminated soil, and polluted water. However, Direct evidence linking maternal lead exposure specifically to childhood cancer in Libya is limited[30].

Ingeneral,Libya faces significant healthcare challenges, including a lack of comprehensive cancer registries and inadequate healthcare services, which can impact early detection and treatment of childhood cancers and maternal child health services especially in areas with social conflict [31].

This exploratory study was proposed to explore and introduce the concern to the scientific community to focus on future research. It was part of other investigations on childhood cancer including the epidemiology, cancerdata quality, and oncology health services in the pediatric hospital in Benghazi. However, due to the small sample size which may be prone to selection bias of mothers, our results cannot be generalized and are limited by recall or reporting bias. Despite of small sample size of this convenient sample, and being a descriptive with lack of a control group, it may give an initial indicator, and further studies with alternative design, such as a case-control design are strongly recommended. Population-based studies with large sample sizes, adjusting for covariates, and minimizing recall bias andselection bias, contribute to more conclusive findings. More importantly, Causal inference is based on a comprehensive view of all evidence available on subtypes of cancers. In consideration of geographical patterns of childhood cancer, as majority of mothers were from Benghazi. This may facilitate further investigations to build hypotheses on other underlying causes that have not been covered in this study.

In conclusion, maternal risk factors for childhood cancer are multifactorial. Understanding the associations of these factors is crucial for developing preventive strategies and interventions aimed at reducing the risk of childhood cancers and more investigations are recommended. Enhancing maternal and childHealth. Implementation of a national registry of maternal comorbidities to follow-up mother’s health during pregnancy. Health education programs are needed to increase mother awareness about the risk of childhood cancers.

Acknowledgment

The author expresses her gratitude to undergraduate students for their contribution in data collection under the author supervision, as a part of their graduation project namely, Aisha H, Mabroka A, Rabha M, Smah E, and Rodina A, at the Department of Health Services Administration, faculty of public health. Thanks are extended to the administration of the pediatric hospital in Benghazi for official permission and  facilitating data collection.

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