Regarding the gestation age, the newborns were grouped as extremely premature (below 28 weeks), early premature (28-32 weeks), moderate premature (32-24 weeks), lately premature (34-36 weeks), and term newborns (37 weeks or more). The malformations were divided into major and minor anomalies.

The data were collected using the Excel program and were processed with SPSS 25 variant statistic program. A p value was considered statistically significant when p≤0.05.

Results

A percentage of 80.56% of newborns with malformations were born at term, much more than those without this type of pathological condition (61.24%). Similarly, 6.2% of infants without anomalies were extremely premature and only 0.69% of infants with intrauterine development anomalies were born below 28 weeks. It has been observed a significant statistical difference with Chi-square Test between the presence of development anomalies and gestational age, a higher percentage of newborns with a normal gestational age in the group of infants with malformations than in the group without these anomalies, but with other pathologic conditions (c²=16.386; p=0.003; Phi and V Crammer’s coefficients = 0.245).

Minor renal malformations were found in 5.56% of the newborns with anomalies (Figure 1; five males and three females), all being born at term, half of them by a caesarean section. There were identified 50% of these patients during pregnancy with a suspicion of minor renal anomalies. Also, 71.43% of patients with this diagnosis had their mother living in urban areas.

From our results, 37.5% of the patients with minor renal malformations and 4.41% of the newborns with other anomalies came from a mother with diabetes (Figure 2). A Chi-square test was applied to verify a possible significant statistical difference between the newborns with minor renal defects and those with other anomalies. The results were positive, the association between diabetes and minor renal anomalies being valid, with p<0.001 (c²=14.118; Phi and V Crammer’s coefficients = 0.313).

It has been found, from our data, that more newborns with minor renal defects (37.5%) than those with other development anomalies (4.41%) came from a mother with cancer in the past (Table 1). The association is moderate, with p<0.001 (c²=14.118, Phi and V Crammer’s coefficients = 0.313).

Referring to major renal defects, 15.28% of newborns from the group with development anomalies had this pathology. Most women who gave born to newborns with major renal defects came from urban area (88.24%). It has been proven a significant statistical difference between major renal anomalies and living in urban areas (c²=4.872; p=0.027). Almost all (90.9%) of newborns with major renal defects were born at term, 77.78% of them being born by a caesarean section. A significant part of major renal anomalies (77.27%) were diagnosed during pregnancy, this proportion being significantly higher than in other types of malformations (c²=20.743; p≤0.001).

In the group of newborns with renal anomalies, there were included two cases of in vitro fertilization (IVF). These two patients had a major renal anomaly, so we note IVF as a possible risk factor for major renal defects. Indeed, further analyses on more IVF cases are required to confirm a possible statistical association.

Although there is not a confirmed statistical association, we observed that women who gave birth to newborns with major renal anomalies (comparing with those who gave birth to infants with other anomalies) had a higher predisposition to drink alcohol (p=0.142). Moreover, 17.65% of mothers who have an infant with major renal defects were drinking alcohol, compared to 6.93% of them with this behavior, but with a newborn with another type of anomalies.

There was one case of major renal anomaly with a particular condition (the mother had also a kidney diseases). Although there is no association between renal malformations in newborns and mothers with kidney diseases, it is worth mentioning a possible risk of developing a major renal anomaly if the mother has a pathological kidney condition.

Discussion

Since the beginning of the 1990s, it has been recommended at least two ultrasound scans to identify different types of embryological malformations⁽⁶⁾. The overall rate of identification for renal malformations is about 55% in most countries⁽⁷⁾. This percentage is similar to the one from our study for minor renal anomalies, and the rate of detection for these with major renal development impairment was even higher. An important aspect for a lower identification rate for minor renal anomalies could be the fact that these defects are sometimes transient and other times they are getting worse⁽⁸⁾. Thus, a better follow-up may increase the rate of detection for minor renal impairments.

A study conducted by Moore et al. on metropolitan Atlanta residents suggested that alcohol consumption in moderate doses during pregnancy may lead to renal agenesis or hypoplasia in infants⁽⁹⁾. Our results suggest the same, more women who drink alcohol having a higher chance to give birth to an infant with major renal anomalies than those who do not consume alcohol.

Similar to Zhong-yi Li et al.⁽¹⁰⁾, a higher prevalence of congenital anomalies of the kidney and urinary tract was described among infants whose mothers lived in urban areas. This can be attributed to a higher awareness of the antenatal care among women in urban areas, but also due to environmental exposures that could generate diverse malformations.

Banhidy et al. suggest an important association between type 1, type 2 or gestational diabetes and congenital urinary tract anomalies⁽¹¹⁾. Other studies concluded that maternal diabetes is a strong risk factor for renal agenesis^(12,13). We also found a significant association between the presence of maternal diabetes and the risk of developing minor renal impairments.

A case-control analysis performed in Washington state by Shnorhavorian et al., using discharge records, showed that maternal renal disease was linked with a five-fold increase in the risk of kidneys anomalies, but also with a four-fold increase in the risk of ureter, bladder and urethra anomalies⁽⁵⁾. From our data, we concluded that the infant with major renal anomaly could develop this condition due to the mother’s kidney disease.

Hays et al. reported a higher prevalence of CRD at lower gestational ages⁽¹⁴⁾. In our study, it was found a higher prevalence of preterm births in the control group, possible due to other pathological conditions associated. A case-control study conducted in Taiwan by Tain You-Lin et al.⁽¹⁵⁾, using national births registry, mentioned as risk factors for CRD the maternal gestational diabetes, maternal thalassemia/hemochromatosis, poly- or oligohydramnios, prematurity and being a boy. We also found a higher incidence of minor renal anomalies among the male sex. A higher incidence of caesarean section was observed for newborns with major renal anomalies than for those with minor renal defects. Polyhydramnios and oligohydramnios can be more severe if a major renal anomaly is present, so a caesarean section is often required for the safety of delivering.

The association between mothers with a personal history of oncologic diseases and CRD in infants was statistically demonstrated in our study, but the reason for this is still debated in medical literature. It is well known that radiotherapy and chemotherapy have a teratogenic effect in the first trimester^(16,17). Other factors for generating CRD in infants who have mothers with oncological problems could be due to a similar mechanism of maternal thalassemia or hemochromatosis. A Japanese cohort study also described an increased risk for developing renal anomalies in infants whose mothers have oncological diseases⁽⁴⁾.

Conclusions

Major renal anomalies are diagnosed in the prenatal period in a higher proportion than minor renal impairment. Alcohol consumption is a risk factor for major renal anomalies. Mothers living in urban areas and those who have diabetes or a personal history of oncological or renal diseases have a higher prevalence for infants with urologic anomalies. Caesarean section is more often required for infants with major renal defects and less needed for infants with minor impairments. Males have a higher incidence for minor renal anomalies than females. 

Conflict of interests: The authors declare no con­flict of interests.