Discussion
Congenital diaphragmatic hernia (CDH): CDH refers to a defect of the diaphragm formation that often presents in the neonatal period with moderate to severe respiratory distress.[7]
CDH has a reported incidence that ranges between 0.7 and 2.61 in 10,000 live births, depending on the geographical area and the period examined.[8], [9], [10] From 2009 to 2019, 395 CDH cases were reported in South Brazil, with an incidence of 0.93 cases per 10,000 live births. The highest incidence was in Rio Grande do Sul (0.97). Santa Catarina was in second (0.94), and the lowest incidence was in Paraná (0.87)
The mean maternal age in CDH cases was 27.8 years and it was 27.3 among non-CDH mothers. There was no association between maternal age and CDH (p=0.38). Our findings were similar to others that did not find any association between maternal age with CDH. [3], [11] On the other hand, a systematic review from Paoletti et al. [10] found that maternal age >35 years was significantly associated with the disease, but the age evaluation analyzed only five papers, none of them from South America. Yang et al. [12] found relative risks were elevated by at least 50% in maternal age >35 years, but only for non-isolated CDH cases.
Most CDH mothers had eight or more years of formal education (n=318/394, 80.7%), were married or in a stable relationship (n=216/389, 55.5%), had seven or more prenatal consultations (n=301/392, 76.8%) and had single pregnancy (n=385/395, 97.5%). No association was found between all these variables and the presence of CDH (Table 2).
There was an association between CDH and birth <37 weeks (p<0.01), and cesarean delivery (p<0.01).
The mean birth weight (BW) for CDH babies was 2794.6 g, while for non-CDH babies was 3189.2 g, there was an association between CDH and lower BW (p<0.01).
The median Apgar 1 and Apgar 5 in CDH cases was 5 and 9, respectively, and in non-CDH babies was 7 and 10. This was also statistically significant (p<0.01).
CDH babies are born at a significantly earlier gestational age (GA), with lower BW and Apgar scores. [3], [11]
Although neither mode nor time of delivery seems to affect the outcome for patients with prenatally diagnosed CDH,[13] children born with this malformation are significantly more often delivered by cesarean section. [11] In this study, we did find an association between surgical delivery and CDH.
There was also an association between CDH and the male sex (p=0.02). Although some studies did not find differences in gender distribution, [11] our finding that males are more likely to have CDH is in general agreement with previous studies. [10], [12], [14] According to Woodbury et al., [14] the rate ratio for males is 1.5.
While some papers did not find an association between maternal ethnicity and CDH, [11] others showed that babies of black descent were less likely to develop the malformation. [10], [12], [14] On the contrary, a previous study from São Paulo state (Brazil) reported a higher prevalence of CDH in babies from black mothers than from other ethnic categories. [3] We found an association between black ethnicity and CDH (when comparing black and non-caucasians; p=0.03) with an incidence of 1.49 cases per 10,000 live births within this subgroup, which could be a peculiarity of our country/region.
Esophageal atresia (EA): EA is the most frequent anomaly of the esophagus and is characterized by a congenital esophageal disruption with or without tracheoesophageal fistula. [15], [16] Diagnosis can be formed during the prenatal scans or, in most cases, at birth, and surgical repair is required in the first few days of life. [16] Its incidence is reported to vary from 0.7 to 4.53 per 10,000 births. [15], [16], [17], [18]
From 2009 to 2019, 200 EA cases were reported in South Brazil. The total incidence was 0.47 cases per 10,000 live births, and it was very similar among all three states (0.48 in Santa Catarina, 0.47 in Paraná and 0.46 in Rio Grande do Sul, all per 10,000 live births).
This lower incidence found in our study (a little under 0.5 cases per 10,000 LB) could be the true incidence in South Brazil, but could also be due to some study. limitations: (1) only live births were included in this study; (2) some publications considered esophageal stenosis as EA; [16](3) the association between EA and other malformations is very common and these cases might have been placed under a different diagnosis in DATASUS; [16], [18], [19] (4) Brazilian protocols recommend that the orogastric catheter is not used in the delivery room, which could delay the diagnosis, and, since our data was based on delivery room information, some cases might have been missed. [20]
The mean maternal age in EA cases was 28.02 years and it was 27.27 among non-EA mothers, and there was an association between EA and mothers > 35 years when compared to mothers 20-35 years (p<0.01). Our findings are supported by other studies that described an elevated relative risk for mothers >35 years, although this is not a consensus. [16], [17]
Most EA mothers had eight or more years of formal education (n=155/200; 77.5%), were married or in a stable relationship (n=108/199; 54.3%), and had seven or more prenatal consultations (n=139/198; 70.2%). No association was found between all these variables and the presence of EA.
There was an association between EA and multiple pregnancies (p=0.04), birth <37 weeks (p<0.01), and cesarean delivery (p<0.01). The association between twin pregnancy and EA has been previously reported, and mortality is greater in this subgroup.[16], [18], [21], [22] Although there is no proven benefit regarding the mode of delivery, [23] cesarean was more commonly performed in South Brazil (n=149; 73,76%), and we found an association between EA and surgical delivery (p<0,01, Table 2). This finding is supported by previous studies. [24]
The mean BW for EA babies was 2441.96 g, while for non-EA babies was 3189.24 g, and there was an association between EA and lower BW (p<0.01). Previous reports also described an association between lower GA and EA. [18], [19] The association between low BW and EA is well established, and this association was also found in our study. There is speculation that the high mechanical obstruction seen in EA may lead to intrauterine growth retardation from decreased absorption of amniotic fluid since its proteins are believed to be absorbed by fetal intestines and used in fetal protein synthesis. [17], [18], [19]
The median Apgar 1 and Apgar 5 in EA cases was 8 and 9, respectively, and in non-EA babies was 9 and 10. This difference was statistically significant (p<0.01).
Although the majority of neonates were male (n=108, 53,46%) and previous papers described significant differences in EA incidence between races, we found no statistical significance regarding sex (p=0.12) or race (p=0.76). [16], [17], [18]
Gastroschisis (GS): GS is a congenital anomaly of the anterior abdominal wall associated with bowel evisceration that requires surgical correction and is generally associated with prolonged hospitalization, high costs, and high neonatal morbidity. [25], [26]
From 2009 to 2019, 1,225 GS cases were reported in South Brazil, with an incidence of 2.87 cases per 10,000 live births. The highest incidence was in Santa Catarina (3.01); Rio Grande do Sul was in second (2.96), and the lowest incidence was in Paraná (2.73).
Worldwide, GS incidence varies from 1.1 cases to 4.49/10,000 live births.[9], [27], [28] Previous Brazilian studies described an incidence of 2.15 cases/10,000 live births in São Paulo, [26] 3 cases/10.000 live births in Rio de Janeiro, and 2.69 cases/10.000 live births in Rio Grande do Sul, all in the vicinity of our 2.87 cases/10,000 live births.
The mean maternal age in GS cases was 20.8 years and it was 27.3 among non-GS mothers, and there was an association between young maternal age and GS (p<0.01).
The association between GS and young maternal age has been frequently documented.[9], [25], [26], [27], [29], [30] In South Brazil, less than 2% of mothers (n=19) were > 35 years old, with an incidence of 0,31 cases/10,000 live births in this age group. When only mothers younger than 19 years are considered, the incidence reaches its highest number, with 8.83 cases/10,000 live births.
GS was associated with fewer years of maternal formal education (p<0.01), single parenting (p<0.01), and a smaller number of prenatal consultations (p<0.01).
No association was found between single/multiple pregnancies and the presence of GS (p=0.46).
There was an association between GS and birth <37 weeks (p<0.01). Anderson et al. [27] found no difference in the length of prenatal care between patients with and without GS. In South Brazil, women pregnant with babies with GS had a significantly smaller number of prenatal consultations, which is worrisome given the complexity of this malformation and the high risk of preterm delivery. [27], [30] Egger et al. [29] found a 5.7 relative risk of premature birth for GS. Indeed, 53.3% of babies with this malformation in South Brazil (613/1150, Table 2) were born <37 weeks of gestation, and there was an association between preterm delivery and GS.
Although cesarean section delivery is not beneficial in GS, [26], [30], [31], [32] most babies with the malformation (1016/1224, 83%, p<0.01) were delivered via cesarean section, and an association between the malformation and mode of delivery was found. Perhaps obstetricians and mothers feel more comfortable with a surgical delivery in the setting of malformations.
The mean BW for GS babies was 2341.2 g, while for non-GS babies was 3189.4 g, and there was an association between GS and lower BW (p<0.01).
The median Apgar 1 and Apgar 5 in GS cases was 8 and 9, respectively, and in non-GS babies was 9 and 10. This difference was statistically significant (p<0.01).
GS is associated with low and very low BW, [27], [30] and we found an association between weight <2500 g and GS. Furthermore, neonates with GS presented lower Apgar scores than neonates without the anomaly.
Analysis by sex (p=0.10) showed no statistically significant difference, as previously reported. [24], [26], [29]
Although no difference was found between GS and non-GS babies regarding race (p=0.96), international studies reported differences in prevalence concerning race/color. [27], [30]
Limitations: Because this study was based on secondary data, the ascertainment of information was conditional on the completeness and accuracy of the available records and the level of clinical detail obtained was limited. Stillbirths were not included due to an error when generating data, which was reported to the website, but the problem was not solved. Despite these limitations, this large population-based study estimates the prevalence and demographic factors associated with CDH, EA, and GS, and extends the limited descriptive epidemiologic information available.