7 Marco teórico
7.4 Un acercamiento al concepto de cultura
The long-term outcome of children with prenatally detected cystic lung lesions is excellent, independent (p>0.3) of the prenatal outcome predictors, and not influenced by the early (respiratory) outcome as observed in my patients survey. This is backed by the following findings. No fatality occurred past infancy. A single child of this study died in the extended neonatal period, at 2 months of age. In the surveyed literature, only four infant deaths were recorded and all of them occurred within 3 months of birth (Table 6; one case excluded because of uncertain detail).
The initial respiratory difficulties improved in the patients of my study, either in the neonatal period (41%), during the first 2 years (34%), or rarely between 2 and 4 years of age (16%). The majority (75%) was completely asymptomatic at last follow-up, 20% had minor residual labored breathing on exertion or infrequent mild asthmatic symptoms, and only three children who had received operations continued to be moderately symptomatic with limited physical endurance (3 years old), frequent pulmonary infections (5 years old), or asthma (12 years old) (Tables 2.2 and 3). To the best of my knowledge, this report of a comprehensive long-term surveillance of a large cohort of fetuses with cystic lung lesions is unique in the literature. Most of the other published reports focused on perinatal outcome. The few examinations of long-term outcomes were performed on small patient numbers or selected cases (Table 6). So far, only one recent study by Kamata et al. [81] presents a comparable long-term study, with a similar follow-up interval (6.9 mean years of Kamata’s study versus 5.9 mean years of my study), but with less than one-half as many patients, compared to my study. As I did, Kamata et al. also observed that respiratory symptoms, such as frequent respiratory tract infections and
asthmatic attacks, improve or disappear with increasing age. In their series only one 7- year-old child who had massive hydrops during fetal life had persistent severe respiratory restrictions. Two more children are reported by other authors to have pulmonary sequelae and asthma with recurrent pneumonia later in life [103, 128]. All other children with fetal cystic lung lesions who were followed long-term are reported to have complete functional recovery after overcoming the critical neonatal period [23] and are doing well at last follow-up [39, 41, 73, 104]. However, using ventilation and perfusion lung scintigraphy to evaluate the children’s lung functions, Kamata et al. discovered a significant decrease of lung ventilation and lung perfusion in patients who have had a large fetal mass (low L/T), prenatal hydrops, or required a lobectomy [81]. This suggests that lung scintigraphy appears to be a sensitive method for evaluating even subtle lung function deficits, and it should be applied in future care and research studies of fetuses with lung lesions. In my research, I focused on clinically relevant respiratory symptoms and on the potential interference with the children’s or families’ daily activities. In this regard, all of the 51 surviving study patients were doing fine except for the three above-mentioned, moderately affected children. Furthermore, prematurity-associated non-respiratory problems, such as prolonged difficulties with feeding, weight gain, and GERD, improved to a milder stage mostly by the age of 2 years. Kamata et al. (2006) also observed that failure to thrive is a common complication, but improves with increasing age. They argue that prolonged artificial ventilation, labored respiration, and frequent respiratory tract infections lead to malnutrition, and it may last in patients who have had fetal hydrops, as they experienced with one case [81]. Other major congenital anomalies were seen in 8% (5 of 60) of the patients in my study. This rate is slightly higher than the average anomaly
Discussion Part I 99
rate of 5% of the cases included in Table 6. The explanation for this data is that a few studies in Table 6 did not include cases with major anomalies due to the restrictive referral policy of their tertiary care centers or the exclusion of these cases from their research population [34, 46, 47, 59, 143]. Only 3% of the anomalies were detectable before birth in my 60-patients-series. This percentage is comparable with the average frequency of prenatally detected congenital anomalies of about 2% in ordinary pregnancies, observed in the EUROFETUS and EUROCAT study [98]. The incidence of congenital heart diseases is 11.8:1000 (Table 6) and not significantly elevated in fetuses with cystic lung lesions, compared to a general prenatal incidence of 6:1000 to 12:1000 [71]. The computed incidence from the reports summarized in Table 6 is 6.9:1000 for renal agenesis and 2.1:1000 for trisomy 18 in the fetal lung lesion population and it is surprisingly high. This is in contrast to a reported incidence of about 0.3:1000 of each, renal agenesis and trisomy 18, in regular pregnancies [27, 86, 115, 151]. In my 60- patients-series, one unilateral renal agenesis (in association with a Mayer-Rokitansky- Küster-Hauser syndrome) and one ultrasonographically questionable bilateral renal agenesis (not confirmed with an autopsy report) were found, but no cardiac anomalies (only 10 newborns with non-structural, transient cardiac symptoms) or trisomy 18 cases. In summary, the long-term outcome of fetuses with cystic lung lesions, such as CCAM or BPS, is excellent. Most children are postnatally asymptomatic and the other survivors grow out of their initial respiratory symptoms by early childhood at the latest. Only a few exceptional cases remain with prolonged respiratory or non-respiratory anomalies.
There is a significant difference between the long-term outcome of fetuses with CCAM or BPS and the long-term outcome of fetuses with congenital diaphragmatic
hernia (CDH). Neurodevelopmental delay, hearing loss, and growth failure is frequent in children with severe fetal CDH, as recent follow-up studies on CDH show [33, 111]. Mortality and pulmonary hypoplasia rates are much higher in association with prenatally diagnosed CDH than with CCAM and BPS, despite similar ultrasound impressions of the volume of the mass and the compression of the surrounding normal lung during pregnancy [5, 47, 58, 129]. About 30% of CDH patients require ECMO (extracorporeal membrane oxygenation) after birth, and about 25% of the survivors suffer from long-term chronic obstructive airway disease [77, 105]. Only a single child of the 51 survivors in this study of fetuses with cystic lung lesions had ECMO and did not survive. None of the children of this series and of the reported series had long-term neurodevelopmental delays or hearing loss. Only very few children with very large fetal lung masses or hydrops had prolonged respiratory sequelae, as described in CHAPTER 5.2.4 and discussed above in this CHAPTER 6.1.6. The outcome of fetuses with cystic lung lesions is much better than the outcome of fetuses with CDH.
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