Research & Reviews: Journal of Medical and Health Sciences
MenuISSN: 2319-9865
ISSN: 2319-9865
Berhanu Kindu*, Assefa Agegnehu
Department Biomedical science, Debre Tabor University, Debre Tabor, Ethiopia
Received: 11-Dec-2023, Manuscript No. JMAHS-23- 122908; Editor assigned: 13-Dec- 2023, Pre QC No. JMAHS-23- 122908 (PQ); Reviewed: 27-Dec- 2023, QC No. JMAHS-23-122908; Revised: 03-Jan-2024, Manuscript No. JMAHS-23-122908 (R); Published: 10-Jan-2024, DOI: 10.4172/2319-9865.12.4.002.
Citation: Kindu B, et al. The Patterns and Risks Factors Associated with Birth Defects Among New Borns. RRJ Med Health Sci. 2024;12:002.
Copyright: © 2024 Kindu B, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
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Birth defects are series of abnormalities of infants that occur during the period of pregnancy which are also termed as congenital disorders, congenital anomalies, congenital malformations and congenital abnormalities. The frequently observed birth defects include congenital heart disease, neural tube defects, orofacial clefts, musculoskeletal defects, urogenital problems and Down syndrome. Congenital abnormalities can develop at any time of the pregnancy, from conception to birth. Genetic factors, sociodemographic factors, medical and drug factors, reproductive and obstetric factors, and environmental factors have been implicated in the risk factors of congenital anomalies. The aim of this article is to elaborate the types and risk factors associated with birth defects among new borns. It is important to researchers, health planner, policy maker, governmental and Non-Governmental Organizations (NGOs) working on the issues of birth defect prevention and control; and other stake holders such as health professionals in designing interventional project towards improving child health and reducing morbidity and mortality due to birth defects.
Birth defects; Risk factors; Embryology; Neonate
Birth defects are defined as a series of abnormalities of infants that occur during the period of pregnancy. They are described by different terms like congenital disorders, congenital anomalies, congenital malformations and congenital abnormalities [1]. These disorders are classified as structural, functional or metabolic and can result in critically damaging effects on the lives and health of infants. Terms used to describe the study of these disorders are teratology and dysmorphology [2]. Susceptibility to teratogens varies with the developmental stage at the time of exposure. The most sensitive period for inducing birth defects is the third to eighth weeks of gestation. During this period of pregnancy exposure to teratogens may cause major, minor or both forms of birth defects [2]. Major birth defects are anomalies that have partial or complete organ/organ system absence/defects, resulting in functional, health, and cosmetic effects, which require surgical repair and rehabilitations [3]. Minor birth defects are structural abnormalities, such as small ears, pigmented spots, and short palpebral fissures, are not themselves detrimental to health but, in some cases, are associated with major defects [2].
Birth defects may be detected during pregnancy or be visible at birth or later in life. The problems can occur as isolated or multiple anomalies and can affect any part of the organ system of the developing embryo [4]. The common types of birth defects include congenital heart disease, neural tube defects, orofacial clefts, musculoskeletal defects, urogenital problems and Down syndrome. Birth defects can either be visible, like spina bifida (neural tube defects), orofacial clefts, omphalocele, gastroschisis, and reduction limb defects or invisible, such as heart defects, patent ductus arteriosus, tracheoesophageal atresia, and duodenal atresia [5].
The exact causes of birth defects are unknown. Until the early 1940s, it was assumed that congenital defects were caused primarily by hereditary factors. With the discovery that rubella affecting a mother during early pregnancy caused abnormalities in the embryo, it suddenly became evident that congenital malformations in humans could also be caused by environmental factors. In 1961, observations linked limb defects to the sedative thalidomide and made it clear that drugs could also cross the placenta and produce birth defects. Since that time, many agents have been identified as factors that cause birth defects [2]. Currently, evidences suggested that radiation, drugs, malnutrition, chemicals and genetic determinants negatively affects normal development of embryo from time of conception [6]. Maternal age, maternal history of stillbirth, lack of antenatal care, consanguinity and any febrile illness during pregnancy are also identified as major contributors for birth defects [7,8]. Maternal folate deficiency is one of the common risks for neural tude defect, which can be reduced by folic acid supplementation prior to and during early pregnancy [9,10]. At present, vaccination, dietary intake of folate or iodine, and preconception health care are available options for prevention [11,12].
Birth defects affect not only the life of a child and those of his or her family, but the community as well. As a child with birth defects such as spina bifida, limb defects, orofacial clefts grow older, he or she faces unique economic, educational, medical, health, and emotional issues. Paralysis of the legs and bowel and bladder management problems are common. These problems may affect a person’s health, self-esteem, personal interactions and work, and recreational opportunities. Although medical care has greatly improved the survival rates and quality of life of children with most types of birth defects, the children and family’s life are affected with varying degrees of physical and social challenges today. Stigmatization of birth defects in Kenya has been documented affecting the quality of life of caring families [13].
Worldwide, lifelong disability and mortality of children are the outcome of the adverse effects of birth defects. Approximately 3.3 million children under the age of five die per year, because of birth defects. Furthermore, 303,000 infants die within a month of being born because of birth defects, and 3.2 million live-born children are disabled for life, which have direct effect on children, family, health care systems and communities [14]. Although birth defects are the most serious cause of infant mortality and disability in both developed and developing countries, around 94% of birth defects, 95% of fatalities and 15-30% of hospital admissions of infants and children because of birth defects are in low- and middle-income countries [15].
Worldwide, the prevalence of birth defect varies from region to region. In the United States, it has been expected that birth defects occur in 2.76% of newborns. According to the WHO report on population-based registry in Europe the rate of multiple congenital anomalies was 51 per 1,000 live births every year. Based on the WHO report in 2013, the rates of entire structural and functional birth defects in the regions of Eastern Mediterranean and South- East Asia were 69 per 1,000 live births and 51 per 1,000 live births every year, respectively [3]. The prevalence of birth defects are also varied widely in sub-Saharan African countries. It was found to be 1.43 per 1000 in Gabon and 68.4 per 1000 in South Africa [16,17].
This article provides a detailed description and elaborate on the types and risk factors of birth defects. It is important to researchers, health planner, policy maker, governmental and Non-Governmental Organizations (NGOs) that are working on the issues of birth defect prevention and control; and other stake holders such as health professionals in designing interventional project towards improving child health and reducing morbidity and mortality due to birth defects. It will create awareness for the public about birth defects and its risk factors. It can also extend the existing knowledge and skill of health professionals about the risky exposures based on our context.
Magnitude of birth defects
According to the 2015 report of WHO, worldwide, congenital anomalies were identified to be the causes of death in about 276,000 newborns under one month of age every year [18]. In 2016, the figure increased to 303,000 neonates [19]. Systematic review done in sub-Saharan African countries showed that the prevalence of birth defects was 20.40 per 1,000 births in the general population [20]. According to a study conducted in Gabon in 2017, congenital malformations were significantly lower in rural or semi-rural areas than in urban areas (0.14% or 0.64 % vs. 3.5%; P<0.001) [21]. A prospective study done in northwest Ethiopia in 2018 showed that the prevalence of birth defects was determined to be 1.61% [22]. According to a study done in Addis Ababa and north Ethiopia in 2019, the overall proportion of congenital anomalies was found to be 1.99% (95% CI: 1.89–2.09) i.e. 199 children with congenital anomalies per 10,000 [23].
Patterns/Types of birth defects
The common types of birth defects that are frequently observed include congenital heart disease, neural tube defects, orofacial clefts, musculoskeletal defects, syndrome disorders, cardiovascular defects, urogenital problems and Down syndrome [23]. According to a study conducted in Gabon in 2017, the proportions of the types of birth defects were Central Nervous system 9 (28.1%), Musculoskeletal system 9 (28.1%), Gastrointestinal system 12 (37.5%), Circulatory system 1 (3.1%) and Chromosomal defect 1 (3.1%) [21].
A systematic review done in sub-Saharan African countries suggested that among the types of birth defects in sub- Saharan African countries, the most frequent types of birth defects was musculoskeletal systems defects with a pooled prevalence of 3.90 per 1000, followed by neural tube defects 2.98 per 1000, cardiovascular system defects 2.83 per 1000, gastrointestinal defects 1.50 per 1000, orofacial clefts 1.27 per 1000, unspecified birth defects 0.86 per 1000, urogenital system defects 0.69 per 1000 and Down syndrome 0.62 per 1000 [20].
A cross-sectional study done in northwest Ethiopia in 2018 showed that among the 317 infants diagnosed with birth defects, the most frequent types of birth defect was neural tube defects (32.5%), followed by orofacial clefts (27.1 %), cardiovascular system defects (12%), limb defects (8.8%), digestive and abdominal wall defects (6.6%), unspecified congenital malformation (5.4%), Down syndrome (3.2%), genitourinary system defects (2.8%) [22]. Another study done in Addis Ababa and Northwest Ethiopia, the proportion of neural tube defects, orofacial clefts, masculo-skeletal system anomalies, syndrome disorders, and cardiovascular system problems were identified to be 40.3% 37.7–43; 23.3% 21.3–25.4; 23.1% 20.9–25.2; 8% 6.7–9.4; and 2.6% 1.8–3.4, with a 95% CI, respectively [23].
Factors associated with birth defects
Congenital abnormalities can develop at any time of the pregnancy, from conception to birth. Genetic, sociodemographic factors, medical and drug factors, reproductive and obstetric factors, and environmental factors have been implicated in the etiology of congenital anomalies, therefore the embryo and the fetus have to adapt, at a molecular and transcriptional level, to various changes in their cellular milieu [24]. The factors that are implicated to cause congenital anomalies are reviewed as follows:
Genetic factors: The genetic mechanisms associated with BDs have been addressed through studies on associations between risk of birth defects and variants in genes involved in folate metabolism, chosen because of the protective effect of folic acid on birth defects. A small proportion of BDs are associated with known genetic syndromes (Meckel syndrome, and aneuploidy conditions, such as Trisomy 13 and Trisomy 18). Non-syndromic birth defects are also thought to have some genetic basis as evidenced by a 2 to 5% risk of recurrence for mothers with a previous birth defect-affected birth, a 50-fold increase over the general population risk. In addition, consanguineous marriages, a positive family history has been associated with an increased risk of birth defectaffected pregnancy [25].
A population based case-control study conducted in Shanxi province of Northern China showed a history of a previous birth defect-affected pregnancy (OR 5.27, CI 0.98- 28.3) was significantly associated with birth defects [26]. Another hospital-based study conducted at Riyadh and Algeria showed that consanguineous marriage was observed among cases (39.1% and 30%) respectively [27,28].
Socio demographic factors: Various studies have suggested that birth defects risk is higher among families of lower socioeconomic status. Nutritional deficiency due to poverty and poverty related problems could predispose these mothers to BDs affected pregnancy and also maternal age (being young and old), parental low educational status, female gender of the offspring, occupational and residential exposure to chemical pollutants are also associated to birth defects [25,26,29]. Hospital based case–control study conducted at Genoa, Italy, shows that maternal low educational level (OR=4.87, CI, 2.38–9.97), median annual family income (OR=3.35, CI, 1.34– 8.34), maternal age < 25 years (OR=3.36; CI, 1.89–5.36) and >35 years (OR=5.21, CI, 2.42–11), second and third birth order (OR=2.15, CI, 1.25- 3.6) and (OR=3.93, CI, 1.69–9.17) respectively was among the significant risk factors [29].Northern china studies also showed birth defects are associated with a primary school education or lower (OR 2.32, CI 1.09- 4.97) [26]. According to study done in Riyadh and Algeria hospitals female gender of offspring were (36.6% and 70%) respectively was associated to birth defects [27,28].
Maternal nutrition and folic acid consumption
Among the most notable environmental risk factors for birth defects is maternal pre-pregnancy obesity. Studies showed that being overweight in women was significantly associated with an increase of birth defect’s rate. It is believed that glucose homeostasis plays an important role in the birth defect; at the time of neural tube closure, mothers with poorly regulated glucose levels are likely to have an altered intrauterine environment leading to abnormal organogenesis. Greater mean daily consumption of sucrose-containing and high-glycemic index foods was recently shown to be associated with an increased risk of birth defects, especially among obese women [28,30]. Folate status plays a key role in determining the risk of birth defects. Folates are integral to intracellular one carbon metabolism, which produces pyrimidines and purines for DNA synthesis. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus. Maternal supplementation with folic acid during pregnancy reduces birth defects frequency whereas reduced serum folate and/or elevated homocysteine (an inverse indicator of folate status) is observed in some mothers of birth defect affected fetuses, and is considered risk factors for birth defects. Folic acid may not reduce birth defect risk to the same degree in all racial/ethnic groups, suggesting that a genetic component may be involved [25,31].
According to a comprehensive article review of maternal and fetal risk factors associated with birth defects, such as, periconceptional folic acid deficiency, and effects of folic acid supplementation and fortification on rates of birth defects, periconceptional vitamin B12 deficiency maternal autoantibodies to folate receptors, are an important cause of birth defects. About 70% of birth defects in humans are folate-sensitive and can be prevented by 4 mg/day periconceptional folic acid supplementation. The relative risk estimate for the women who were at high risk of having a pregnancy with birth defect because of a previous affected pregnancy and were allocated to take folic acid was 0.28, indicating a 72% protective effect (RR, 0.28; 95% CI, 0.12–0.71) [32].
A case-control studies conducted in Italy and Algeria shows that significant association to birth defects was observed in mothers who didn’t take pre-conception folic acid (OR=27 CI, 9.31–78, and 86%) respectively [28,29]. Another study conducted in Riyadh shows that significant protective effect of periconceptional folic acid consumption both prior to conception (OR 0.02, CI 0.00- 0.07) and during the first 6 weeks of conception (OR 0.13, CI 0.04-0.39). According to study conducted in Iran, maternal obesity (OR: 5.4, CI: 1.3-21.8) was significantly associated with birth defects [33]. A six-year period hospital-based case-control study conducted among all pregnancies with birth defect affected newborns (n=91) in Kasha, center of Iran, indicated that maternal obesity (OR: 5.4, CI: 1.3-21.8) was significantly associated with birth defects [33].
Maternal reproductive history
Studies shows that maternal reproductive histories (history of abortion, still birth, early neonatal loss) are associated risks. Parity has also shown to influence birth defects risk with being highest number of births or an increasing risk with increasing parity [25,34]. According to a 4-year period case-control study conducted at King Khalid University Hospital, Riyadh shows that significantly higher proportion case mothers had, history of stillbirth (case to control ,16% VS. 4.1%, P=0.02), neonatal losses (4.2%) [27]. A six-year period hospital based case-control study conducted among all pregnancies with birth defects affected newborns (n=91) in Kashan, center of Iran, indicated that maternal history of abortion (OR: 4.9, CI: 1.9-12.8), was significantly associated with birth defects [33].
Chemical exposure
Chemicals used as pesticides (insecticides, herbicides, and fungicides) can cross the placenta and impact embryonic development. In animal studies, these chemicals have been shown to alter cell proliferation and differentiation during embryonic development and lead to excessive cell death that impacts the normal development of body parts. Pesticide exposure can occur in both the home and the workplace [35]. According to Italian study use of pesticides or solvents (OR=10.62, CI, 1.23 91), residence near waste sites or polluting industries (OR=3.57, CI 1.54– 8.29) were proved to be a risk factor for birth defects [29]. Maternal exposure to pesticides such as endosulfan, DDT and Dichloro-Diphenyl-Dichloroethylene (DDE) was linked to fetal neural tube defects, with mothers delivering affected neonates reported to have 11.3 times greater chances of been exposed to DDE levels above median concentration of controls [36].
Maternal fever/febrile illness
Maternal hyperthermia can arise from either febrile illnesses or external exposure to heat, such as prolonged period’s use of hot tub or sauna. A recent meta-analysis evaluated that the birth defect risk was increased almost three-fold in cases of maternal fever during the first trimester. And also strongly implicated that maternal fever in early pregnancy as a risk factor for birth defect-affected pregnancies [37]. Although it has been proposed that hyperthermia-induced birth defects may arise from changes in metabolism, research indicates that it is the heat that adversely affects development, likely as a result of increased cell death, decreased proliferation, disruption of gene expression, and damage to the embryonic vasculature, leading to induction of apoptosis, inhibition of proliferation/delayed differentiation [38]. A population based case-control study of fetuses and live born infants with birth defects conducted in California showed that, maternal fever or febrile illness episode in the first trimester was associated with an increased risk for having a birth defect-affected pregnancy (OR 1.91 CI, 1.35–2.72) and (OR 2.02 CI 1.2-3.34) respectively but risks were lower among women who used a fever reducing medication (approximately 95% used antipyretic) [39]. Study of northern china shows that history of a fever (OR 3.36, CI 1.68, 6.72), and use of antipyretic drugs (OR 4.89, 95% CI 0.92, 25.97) is associated to birth defects [26].
Maternal medical and drug factors
Maternal pregestational diabetes mellitus is an important risk factor for the development of malformations; its teratogenic effect may be due to embryonic exposure to elevated glucose concentrations. Hyperglycemia has been shown to inhibit the uptake of myo-inositol, which is essential for embryonic development during gastrulation and neurulation stages of embryogenesis. It has been found to cause a 2-fold to 10-fold increase in risk of malformations among the offspring of affected women, relative to the general population [31]. Maternal epilepsy is associated with a 1% to 2% risk for offspring with birth defects and an overall two- to three-fold increased risk for congenital anomalies in the offspring. This risk is considered to be due to anticonvulsant use, in particular valproic acid and carbamazepine [25]. Other factors including use oral contraceptives, medical illness (like hyperthyroidism), and use of anti-seizure drugs may also predispose offspring to birth defects [25,39].
Maternal life style
Maternal life style factors like alcohol consumption, caffeine consumption, smoking and external exposure to tobacco smoke are associated to birth defects [35]. Maternal caffeine consumption, smoking and external exposure to environmental tobacco smoke have also been studied with respect to risk for birth defect-affected pregnancy. Meta-analyses review indicate that maternal smoking confers a moderately increased birth defects risk in cases of maternal environmental tobacco smoke exposure [37]. Both smoking and environmental tobacco smoke are associated with decreased serum folate levels [38].
According to hospital based study conducted in Italy high caffeine intake (≥ 3cups per day) (OR=7.78, CI, 4.02– 15.05), maternal smoking habits (OR=1.91, CI 1.16–3.14) and alcohol intake (OR= 3.69, CI, 2.12–6.42) were proved to be a risk factor for birth defects [34-38]. In addition to this northern china study indicated that daily passive exposure to cigarette smoke (OR 1.60, CI 0.94, 2.73) was associated to birth defects [26,39-42].
Birth defect causes serious disability and even fatal, that affects the new generation. Although, it touches all the global population the middle- and low-income countries are most affected. It is a direct cause for neonatal and perinatal mortality rate globally. Therefore, pre-conception maternal screening for genetic factors, medical illness and nutritional supplement is important for child bearing women. As well as pregnant women should be assessed for folic acid supplementation, appropriate drugs for illnesses, chemical/radiation exposure and the maternal lifestyle during their antenatal care. Even though, some of the factors that cause birth defect are identified, yet conducting experimental and clinical trial researches are needed to know more on the causes and to decrease its burden worldwide.
There is no conflict of interest on this work.
No funds are gained on the behalf of this article work.
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