Study of Association between Fetal Central Nervous System Congenital Anomalies and Renal Congenital Fetal Anomalies

Conclusion

CNS anomalies were commonly associated with congenital renal anomalies. Maternal age, gestational age, and fatal gender were analysed as potential factors for combined CNS and renal anomalies. Maternal age was the only parameter to show a statistically significant difference among the groups, where isolated CNS anomalies were more prevalent among pregnancies at a relatively older maternal age.

Conflict of interest: None.

Acknowledgments: We acknowledge all participants included in this investigation.

Introduction

Congenital fetal anomalies include metabolic abnormalities and are postnatal structural or functional deviations from normal. These anomalies might be the consequence of flawed embryogenesis or inherent flaws in the growth process. Birth defects may be isolated or combined in a syndromic fashion, and they can also be a major factor in a newborn's impairment or even death. ⁽¹⁾

Prenatal care primarily intended to detect congenital fetal abnormalities A healthy baby's postnatal result is the main justification for using ultrasonography throughout pregnancy. Congenital anomalies include a variety of risk factors, including maternal advanced age, a prior anomalistic infant, a family history of abnormal births, consanguinity, maternal illnesses, drug addiction, virus infections, and ionizing radiation exposure. Birth defect identification may serve as the cornerstone of regional health records for use in preventative initiatives in the future. ⁽²⁾

At 12- 14 and 18–22 weeks of pregnancy, prenatal screening utilizing ultrasonography for the diagnosis of fetal malformations should begin. Although routine fetal anomalies scans are very helpful in detecting fetal anomalies, they do not always reveal all anomalies because not all anomalies are visible at the time of the scan when the ultrasound tool was used. Additionally, the scan itself is operator dependent and heavily dependent on the effective machines that are currently on the market. Due to various factors, such as oligohydramnios or maternal obesity, certain fetuses are difficult to scan clearly. ⁽³⁾

Patients and Methods

The present study was a cross sectional observational prospective study, that was conducted at Al-Minia University Maternity Hospital, Department of Obstetrics and Gynaecology, Fetomaternal unit, which is a tertiary governorate maternity hospital that covers 9 local areas with people about 5.5 million and this hospital accept referral from all governorate hospitals. The study extends from 2021 to 2022, Methodology: The study was carried out according the general ethics and principles that approved by the department committee.

Our study consisted of three steps: Step 1; Ascan surveys for patients with cranial abnormalities will cover the following information: Examining the integrity and normal form of the skull, as well as measuring the biparietal diameter and head circumference Measurement of the anterior and posterior horns of the lateral ventricles, as well as examination of the cerebral ventricles, choroid plexuses, midbrain, and posterior fossa (including the cerebellum and cisterna magna).

Additionally, an ascan survey is performed on patients who have been referred for kidney and urinary tract abnormalities. This survey will look for less frequent anomalies such vesicouretral reflux as well as more severe malformations like multicystic dysplastic kidney and bilateral renal agenesis.

Step 2; classifying the patient into three categories: group 1 includes those with mixed central nervous system and renal malfor-mations; group 2 includes those with isolated cranial anomalies; and group 3 includes those with isolated renal congenital fetal defects. Step 3; Compare groups 1 and 2 to get the overall association percentage. Step 4: To determine the degree of correlation, each cranial aberration will be matched to a renal anomaly. Each connection will be related to the baby's gender, gestational age, and patient age.

Statistical analysis:

The Shapiro-Wilk test was used to determine if the data distribution was normal. SPSS Version 22.0 was used to determine the description of means, standard deviation, medians, and interquartile ranges for quantitative data, and frequencies and percentage for qualitative variables (IBM Corp, Armonk, NY). Comparing categorical and numerical variables was done using the chi-square test and the Kruskal-Wallis test, respectively. A P value of less than.05 was regarded as statistically significant.

Results

Our research included 150 pregnancies in total. Table 1 summarizes the maternal character-ristics of the entire study group. The study group was divided into three categories according to the congenital anomalies identi-fied by prenatal ultrasonography, including: Group A: isolated CNS anomalies (N = 50) and Group B: isolated renal anomalies (N = 50)

As demonstrated in Table 2, a total of 11 CNS anomalies in 100 fetuses were identified. Fifty fetuses had isolated CNS anomalies and another fifty had CNS anomalies associated with renal anomalies.

Overall, the most common congenital anomalies were ventriculo-megaly and anencephaly which were reported in 27 (27%) and 17 (17%) fetuses, respectively. On the other hand, the least frequent congenital anomaly was ACC (agenesis of the corpus callosum), which was reported in one foetus representing 1%. Regarding the presentation of each CNS anomaly as an isolated or combined anomaly, no statistically significant difference was observed (Chi-square test, P = .880).

As demonstrated in Table 3, In 100 fetuses, nine kidney abnormalities in all were found. 50 fetuses had renal malformations that were isolated, while another 50 had renal defects that were linked to CNS anomalies. Cystic kidney diseases, such as multi-cystic dysplastic kidney (MCDK) and autosomal recessive polycystic kidney disease (ARPKD), were the most prevalent renal congenital anomalies overall (39 percent), followed by pelviureteric junction obstruction (PUJO), which was reported in 17

(17 percent) fetuses. Horseshoe kidney and malrotation, on the other hand, were the least common congenital defects, accounting for 4% and 1%, respectively. No statistically significant difference was found between any renal aberration's appearance as a solo or combined anomaly (Chi-square test, P =.995).

As shown in Figure 1, Anhydramnios affected 52% of pregnancies, oligohydramnios affected 24% of pregnancies, and normal amniotic fluid content affected 24% of pregnancies. Bilateral MCDK, ARPKD, PUV, bilateral renal agenesis, and megacystis were all linked to anhydramnios. Oligohydramnios was cone-cted to unilateral renal agenesis and PUJO. Anomalies such as unilateral MCDK, VUJO, horseshoe kidneys, and malrotation were linked to normal amniotic fluid volume.

Table 4 showed the patterns of associations between several reported CNS abnormalities. It was shown that ventriculomegaly (26%) anencephaly (29%) myelomeningocele (30%) arachnoid cyst (25%) DWM (20%) and encephalocele (20%) all often co-occurred with cystic renal abnormalities (9 percent). Holopro-sencephaly (67%) encephalocele (36%), micro-cephaly (27%), meningocele (25%), ventriculo-megaly (15%), arachnoid cyst (13%) myeloma-ningocele (10%), and anence-phaly (10%) were all often associated with obstructive renal abnormalities (6 percent). Renal agenesis was shown to often co-occur with arachnoid cyst (13%) anencephaly (12%), and ventriculo-megaly (4%). (8 percent). SCT (33 percent), myelomeningocele (10 percent), anencephaly (6 percent), and ventriculomegaly were all shown to have a similar connection with megacystis (4 percent). Ventriculomegaly was the sole condition related with morphological abnormalities (7 percent). The only way ACC was described was as a single CNS malfunction.

As demonstrated in Table 5, maternal age was the only parameter to show a statistically significant difference among the groups, where isolated CNS anomalies were more prevalent among pregnancies at a relatively older maternal age (Kruskal-Wallis test, P = .000).

Discussion

The Department of Obstetrics and Gynecology at Al-Minia University's Maternity Hospital carried out this cross-sectional observational prospective research. Study period runs from 2021 to 2022. The research population was split into three groups based on the congenital abnormalities detected by prenatal ultrasound:

Regarding CNS anomalies, a total of 11 CNS anomalies in 100 fetuses were identified. Fifty fetuses had isolated CNS anomalies and another fifty had CNS anomalies associated with renal anomalies. Overall, the most common congenital anomalies were ventri-culomegaly and anencephaly which were reported in 27 (27%) and 17 (17%) fetuses, respectively. On the other hand, the least frequent congenital anomaly was ACC (agenesis of the corpus callosum), which was reported in one fetus representing 1%. Regarding the presentation of each CNS anomaly as an isolated or combined anomaly, no statistically significant difference was observed (Chi-square test, P = .880).

Our results were supported by study of Shawky et al.,, ⁽⁴⁾ as they have categorized the CNS anomalies detected in their study, where they found out that the most detectable anomaly is Ventriculomegaly (43%) followed by these anomalies in descending manner, anencephaly (29.1%), encephalocele (11.6%), spins bifida (4.7%), Dandy walker syndrome (4.7%), holoprosencephaly (3.5%), isolated vermis hypoplasia (2.3%) and the least represented CNS anomalies was Intracranial Haemorrhage (1.2%).

Similarly, Tan et al., ⁽⁵⁾ 365 fetuses were found to have CNS abnormalities prenatally throughout the course of the 10-year research, with a mean gestational age of 24.657.37 weeks upon diagnosis. The most frequent CNS anomaly identified during prenatal testing was ventriculomegaly (23.36 percent).

These order and representing percentage in CNS anomalies disagree with Shawky & Sadik,⁽⁶⁾ as the order in CNS anomalies were Neural tube defect (29%), Microcephaly (21%), Hydrocephalus (18%), Cranial cerebrovascular anomalies (11%) Cerebral defects (7%) Neuroectodermal anomalies (7%).

The present study showed that 50% had appropriate for gestational age (AGA) fetal biometric measurements, 29% had large for gestational age (LGA) measurements, and 21% had small for gestational age (SGA) measure-ments. LGA BPD and HC were reported with ventriculomegaly, encephalocele, and DWM (Dandy Walker malformation). SGA measure-ments were reported with anencephaly, microcephaly, and holoprosencephaly. Fetuses diagnosed with meningocele, myelomenin-gocele, arachnoid cyst, SCT (sacrococcygeal teratoma), and ACC had AGA biometric measurements. By studying the distribution of CNS congenital anomalies across both genders, ventriculomegaly, microcephaly, myelomenin-gocele, arachnoid cyst, DWM, and ACC are more prevalent among male fetuses, while anencephaly, encephalocele, meningocele, SCT, and holoprosencephaly were more prevalent among females. There was no statistically significant difference was detected between male and female fetuses in the overall incidence of CNS anomalies (Chi-square test, P = .061).

Our results were supported by study of Shawky et al., ⁽⁴⁾ as they reported that the gender of baby in this study had no impact on the prevalence of CNS anomalies as the ratio nearly (1:1). The mean of Gestational age was 28 weeks that had no influence on the prevalence of the anomalies.

In the study of Aydın et al., ⁽⁷⁾ The average birth weight was 3060 g, the average gestational week was 37.9, and the average APGAR score at the fifth minute was 8.8 g. Seven (6.5%) of the pregnancies were the result of in vitro fertilization (IVF); the rest were spontaneous conceptions (93.5 percent). There were 69 newborns, of whom 39 (36.2%) were female and 69 (63.8%) male.

A total of nine kidney abnormalities were found in 100 fetuses, according to the results of the present investigation. 50 fetuses had renal malformations that were isolated, while another 50 had renal defects that were linked to CNS

anomalies. Cystic kidney diseases, such as

multi-cystic dysplastic kidney (MCDK) and autosomal recessive polycystic kidney disease (ARPKD), were the most prevalent renal congenital anomalies overall (39 percent), followed by pelviureteric junction obstruction (PUJO), which was reported in 17 (17 percent) fetuses.

The least common congenital defects, on the other hand, were the horseshoe kidney and malrotation, which represented 4% and 1%, respectively. No statistically significant difference was found between any renal aberration's appearance as a solo or combined anomaly (Chi-square test, P =.995). The bladder function was normal in 48% of fetuses. In 36% of fetuses, the bladder could not be seen. 10% of the population had a tiny bladder, whereas 6% had an enlarged bladder. Unilateral MCDK, PUJO, VUJO, unilateral renal agenesis, horseshoe kidney, and malro-tation were all related with a normal bladder. In instances of bilateral MCDK, ARPKD, and renal agenesis, the bladder could not be seen. PUV was associated with a small bladder, but megacystis was associated with an expanded bladder.

Our results were supported by study of Isaksen et al., ⁽⁸⁾ they noted that 50 of the 112 individuals had a primary diagnosis of a urinary system abnormality. Of the 50 cases, the renal or urinary tract abnormality was identified in 38 (76%) of them. One instance had a fetus with hydroureter and hydronephrosis, two cases were intrauterine fetal fatalities with urethral blockage and dilated bladder, and 35 were either renal agenesis or different kinds of cystic renal illness.

In the study of Stoll et al., ⁽⁹⁾ the total prevalence of CAKUT at birth during the 26-year research period was 48.4/10,000. The most common CAKUT were hydronephrosis (14.0; 29), renal dysplasia (10.1; 21), renal agenesis (6.6; 14), vesicoureteric reflux (VUR) (5.3; 11), and megaureter (in parenthesis the prevalence at birth per 10,000 and the percentage are reported) (4.5; 9).

In the study in our hands, 52% of pregnancies had anhydramnios, 24% had oligohydramnios, and 24% had normal amniotic fluid volume. Anhydramnios was associated with bilateral MCDK, ARPKD, PUV, bilateral renal agenesis, and megacystis.  Oligohydramnios was associated with PUJO, and unilateral renal agenesis. Normal amniotic fluid volume was associated with unilateral MCDK, VUJO, horseshoe kidney, and malrotation anomalies. In terms of the overall incidence of renal abnormalities, there was no statistically significant difference between male and female fetuses (Chi-square test, P =.081).

According to Okoronkwo, et al., ⁽¹⁰⁾ CAKUT affects 20% of children under the age of 18, with PUV accounting for 36% of the abnormalities. In a study of 13,775 consecutive autopsies, Barakat et al., ⁽¹¹⁾ discovered that 4.6 percent of all males under the age of 18 had CAKUT, and 9.5 percent had it overall. The abnormalities affected the kidneys in 45.1% of cases, ureters in 29.1%, renal vessels in 12.4%, urethra in 5.3%, bladder in 4.8%, and fistulas in 3.3%.

According to Li et al., ⁽¹²⁾, throughout the research period, the average prevalence of CAKUTs born to mothers overall and mothers aged 35 years was both 1.60 per 1000 births (95 percent confidence interval (CI), 1.54-1.66; 95 percent CI, 1.44-1.83, respectively). All women and women who were past childbearing age experienced an increase in the prevalence of CAKUTs over time, though no discernible trends were seen. CAKUTs were more likely to occur in male than female newborns, in multiple births as opposed to singletons, and in urban as opposed to rural settings (odds ratio (OR) 1.27, 95 percent confidence interval (CI) 1.18-1.37). The overall rate of prenatal CAKUT detection was 73.87 percent. At the time of the prenatal diagnosis, the average gestational age was 26.57 8.70 weeks.

Additionally, studies by Groen et al., ⁽¹³⁾, Macumber et al., ⁽¹⁴⁾, and others showed that CAKUTs may be more common in women who are obese, receiving fertility treatments, multiparous, suffering from infectious disorders, or having diabetes when pregnant.

Our results showed that as regard association patterns of different reported CNS anomalies. Cystic renal malformations were found as a common association with ventriculomegaly (26%), anencephaly (29%), myelomeningocele (30%), arachnoid cyst (25%), DWM (20%), and encephalocele (9%). Obstructive renal anomalies were found as a common association with holoprosencephaly (67%), encephalocele (36%), microcephaly (27%), meningocele (25%), ventriculomegaly (15%), arachnoid cyst (13%), myelomeningocele (10%), and anencephaly (6%). Renal agenesis was found as a common association with arachnoid cyst (13%), anencephaly (12%), and ventriculo-megaly (8%). Megacystis was found as a common association with SCT (33%), myelomeningocele (10%), anencephaly (6%), and ventriculomegaly (4%). Morphological malformations were only associated with ventriculomegaly (7%). ACC was only presented as an isolated CNS anomaly.

Maternal age, gestational age, and fatal gender were analysed as potential factors for combined CNS and renal anomalies. Maternal age was the only parameter to show a statistically significant difference among the groups, where isolated CNS anomalies were more prevalent among pregnancies at a relatively older maternal age (Kruskal-Wallis test, P = .000).

Our results were supported by study of Barakat et al., ⁽¹⁵⁾ as they said that 10% of CAKUT patients may have related CNS abnormalities (brain and spinal cord anomalies, meningomyelocele, spina bifida and hydrocephalus). Furthermore, Rimoin et al., ⁽¹⁶⁾ showed that encephalocele, hydronephrosis, spina bifida, and anencephaly may all be linked to bilateral renal dysplasia.

In addition, Lu, et al., ⁽¹⁷⁾ identified five individuals with CNS malformations linked with ureteral and renal problems (thin, hypoplastic, or missing corpus callosum; hydrocephalus or ventriculomegaly; Chiari type I malformation; and tethered spinal cord) (VUR, UPJ abnormalities, bifid and megaureter). Furthermore, according to Barros et al., ⁽¹⁸⁾, CAKUT is linked to 30.4% of embryonic CNS abnormalities, mostly encephalocele.