The present study showed that among infants with CAs, 70.6% were males and 29.4% in females. These results were in agreement with a retrospective study conducted in El Shatby University Hospital [19] which found that males admitted to the surgery unit of the hospital during the years 2009–2011 were more than females.
In the current study, digestive system anomalies and musculoskeletal anomalies constituted 38.0% and 32.9% of the total CAs respectively. They were more than those recorded in a surveillance study conducted in Glasgow and Clyde in 2015–2016 where GIT anomalies constituted only 9% while musculoskeletal anomalies constituted 25% [20]. Different rates might be attributed to the fact that the present study was a hospital-based case series while the other study was conducted using a population-based surveillance program.
Circulatory system anomalies constituted 11% of the total CAs in the current study. The surveillance study conducted in Glasgow and Clyde found that the prevalence of circulatory system anomalies was 13.9% [20], and the EUROCAT records showed even higher figures for circulatory system anomalies (35%) [21]. Genetic disorders and genitourinary anomalies constituted 8.4% and 4.9% of total CAs, respectively, in the studied years. The percent of genitourinary anomalies was much lower than that of the EUROCAT records (24.2% of total CAs) [21]. The difference between the rates might be due to the difference in the methodology used and in exposure to various risk factors.
The case-control study revealed that males were 1.92 times at higher risk of having CAs than females. This result was in agreement with Tennant et al., who found a 15% increased risk of CAs in male infants than female infants in North England (1985–2003) [22].
The current study showed that children with CA were more among mothers aged above 35 years than mothers aged less than 35 years, but this was not statistically significant. A study done in Tanzania in 2013 [23] and a study done in Ain Shams University, Cairo, in 1995–2009 [14] showed a significant association between mothers aged above 35 years and CAs.
The present study showed that infants born to fathers aged 45 years or more were more than those having fathers aged below 45 years. In Knudsen, Danish in 1980–1996, there was no significant association between paternal age and the overall prevalence of CAs but there was a significant association between paternal age and limbs’ anomalies, multisystem syndromes, and Down syndrome [24]. Another study done in California, 1989–2002, showed that there was a significant association between paternal age and some selected CAs [25].
Obese females were at a higher risk of having infants with CAs. Mills et al., in New York 1993–2003 [26], found a strong association between obesity and CHDs. A systematic review concluded a contribution of obesity to certain types of CAs such as NTDs, CHDs, and orofacial defects [27].
The results of the present study agree with other studies that found a high frequency of CAs in infants born to females with a history of oligohydramnios. Oligohydramnios interferes with fetal movement resulting in a cascade of developmental events leading to fetal anomalies [28]. The same observation was seen in the case of polyhydramnios. Some studies indicated that CAs may be a potential cause for polyhydramnios but not the reverse. Some anomalies like oesophageal atresia, duodenal atresia, and some neuromuscular disorders impair the swallowing reflex and increase urine and amniotic fluid production resulting in polyhydramnios [29].
Mothers of children with CAs that gave history of hypertension during pregnancy were significantly more than mothers of the control group. A systematic review by Ramakrishnan et al. (2015), found an association between maternal hypertension and CVS anomalies. The association between treated hypertension and CVS anomalies was stronger than that for untreated hypertension which might suggest that antihypertensive drugs lead to an additional increase in the risk of CAs [30]. There was also a twofold increased history of preeclampsia among mothers of cases in the present study. Nelson et al., in Texas (2012), showed an increased rate of CAs in preeclampsia and suggested that fetal anomalies related to preeclampsia are limited to isolated microcephaly and hypospadias, and both microcephaly and hypospadias are associated with impaired fetal growth in females with preeclampsia [31]. There was also a one and half fold increased risk of CAs in infants born to females who experienced antepartum hemorrhage in the current study. Shawky et al. revealed an association between early antepartum hemorrhage in pregnancy and CAs [14].
Mothers of cases that gave history of taking different types of unprescribed medications were more than mothers of controls. Different studies showed an association between different types of drugs and CAs such as Uziel and Rozental [32] who showed that antiepileptic drug (AED) administration resulted in CNS anomalies and Etemad et al. [33] who found a high frequency of major anomalies, heart defects, and hypoplasia of the midface and fingers, known as anticonvulsant embryopathy, in infants exposed to anticonvulsant drugs in utero mainly AEDs. Yakoob et al., meta-analysis, suggested an increased risk of CVS anomalies, orofacial clefts, and NTDs following intake of oral beta-blockers in the first trimester of pregnancy [34].
History of exposure to chemicals during pregnancy was three and a half folds more among mothers of cases than mothers of controls. Desrosiers et al. [35], in the USA, observed an increased prevalence of NTDs among infants born to women exposed to chlorinated solvents during the peri-conceptional period, but they did not find an association between orofacial defects and exposure to chlorinated solvents. Hjortebjerg et al., in Denmark in the period 2001–2003, observed a positive association between exposure to paint fumes in the first trimester of pregnancy and the risk of CNS and ear, face and neck, and renal system anomalies [36].
Mothers of children with CAs indicated exposure to pesticides during pregnancy much more than mothers of controls. This result agrees with Kielb et al. [37], who found an elevated risk of having an infant with isolated gastroschisis among mothers aged 20 years old or more occupationally exposed to pesticides and with Liete et al. [38] who also found an association between exposure to pesticides and CAs in newborns. On the other hand, Clementi et al. [39] reported that there is no evidence that exposure of mothers to pesticides during pregnancy has any effect on the prevalence of CAs.
The present study showed that there was a significant association between living near strengthening mobile stations and the presence of CAs. Most of the human studies focused on the effects of mobile radiations and mobile base stations on the overall health of human beings. Very limited studies focused on the effect of mobile phones and mobile strengthening stations on the embryo development and CAs. The non-thermal interaction may lead to an increase in the production of reactive oxygen species leading to DNA damage in the sperms [40].
Limitations of the study
Mothers of children with CAs, in their efforts to detect the reasons of the CAs, may be more prone to remember exposure to risk factors than mothers of normal children. In addition, some of the severe CAs may be missed as the newborn may die soon after birth, and some of the mild CAs may not be detected early after birth such as deafness and so the pattern of the type of CAs may not reflect the full picture.
Although it would have been better to calculate the prevalence of CAs, yet it was difficult to obtain the data of the denominator that is why the researchers calculated the frequency of CAs.
Diagnosis of risk factors was reporter dependent, and there was also a lack of standardized measurement of some factors such as oligohydramnios.