Pulmonary hypertension (PH) is a key factor determinant in CDH pathophysiology and requires critical consideration in therapeutic management of the high-risk newborn patient. PH is defined based on pulmonary arterial pressures of > 20 mmHg and the pulmonary vascular resistance indexed to body surface area with gold standard assessment by right heart catheterization studies [4, 12]. However, in newborns with CDH, a simple pressure-based definition is not readily feasible and invasive measurement of pulmonary arterial pressures are not always practical.

In healthy newborns following delivery there is a rapid postnatal fall in pulmonary vascular resistance (PVR) although echocardiographic signs of elevated PVR in the first 24–72 h are still detected and will gradually resolve within some 14 days. Newborns with hypoplastic lungs are more at risk of developing persistent PH over 48 h after birth [6]. Many authors have proposed methods of post-natal assessment of PH in CDH newborns based on a combination of invasive and non-invasive markers such as best OI on the first day of life, N-terminal-pro B type natriuretic peptide (NT-proBNP) and serial echocardiography [8, 13, 14]. OI has been proposed as an indicator of disease severity and a surrogate marker guiding clinical management of infants with PH [15]. OI is calculated as OI = MAPxFiO2 × 100/PaO2 where MAP indicates mean airway pressure and FIO2 indicates fraction of inspired oxygen.

Pulmonary pressures recorded during the first 24 h following birth are considered the most notable dynamic change due to a combination of alterations in newborn pulmonary mechanics compliance and active ventilatory management. Leyens et al. [6] suggested that early dynamics of PH over the first 48h of life are dependent on PH severity. Previous studies examining OI have demonstrated increased survival rates (%) in newborns having an OI < 10 thus affirming utility of OI as predictor of CDH survival [9, 16]. We have observed and studied the dynamics of OI trends during the first 72 h of life in CDH newborns at our Thailand university centre and noted that an initially low and a gradual decrease of OI during the first 72 h following birth can be predictive of survival (Fig. 1).

In management of CDH carefully instituted perinatal care plans are critically required especially for the respiratory system, monitoring of pulmonary hypertension and dealing with cardiac dysfunction. Permissive hypercapnia or ‘gentle ventilation’ has significantly contributed to marked improvements in survival for CDH [17]. The VICI trial found no differences in lung volume recruitment and/or outcome(s) of fatality and bronchopulmonary dysplasia comparing CDH patients who received conventional ventilation vs HOFV [18, 19]. A study from Canada [20] has also reported no differences between HFOV and conventional mechanical ventilation with oxygen dependency and survival in infants with CDH. Guidelines from the European Congenital Diaphragmatic hernia (CDH EURO) Consortium, American Academy of Pediatrics and American Heart Association (AAP/AHA) recommend the routine intubation at birth of all infants with CDH with avoidance crucially of bag-mask ventilation where the prenatal diagnosis is known. Cochius-den Otter et al. have recently proposed a feasibility study examining a ‘spontaneous breathing approach’ in CDH neonates considered to have adequate antenatal lung development [21]. The important point(s) with regard respiratory care management is to prevent ventilator-induced lung injury with peak inspiratory pressure of < 25 cmH2O recommended [19].

Most CDH inborn patients in this cohort study [52/55 (94.5%)] were intubated immediately after birth (Table 2) with only 2 babies noted who were able to breathe spontaneously without the need for respiratory support. Of those patients requiring ventilatory support ie. 29/52 (55.8%) HFOV was later deployed. Significant difference(s) between the OI recorded during the first 72 h of life in the HFOV group and conventional mechanical ventilation patients are highlighted (Table 2). Additionally, we noted significantly a higher pre-operative mortality(%) in CDH patients receiving HFOV (P = 0.02) and also a greater duration period(s) of pre-operative stabilisation required before definitive CDH defect repair (9.1 ± 6.8 days in HFOV vs 3.5 ± 2.4 days in the CMV study group; P = 0.007). Higher OI was observed on operative days in the HFOV patient group (8.3 ± 7.7 vs 2.4 ± 2.0; P = 0.009) (Fig. 2). Furthermore, higher mortality rate was seen in patients who had undergone preoperative HFOV compared to those who were stabilized on conventional mechanical ventilation (58.6% vs 8.7%; P < 0.05) (Table 2).

While a strategy of delayed surgery after stabilization of cardiopulmonary physiology has been broadly accepted there is no overarching consensus at time of writing regarding the optimal timing of operative repair [4, 22]. The CDH EURO consortium proposed varied factors for indications of timing of surgery such as mean arterial pressure(s) should be more than gestational age, pre-ductal saturation levels of 85–90% on FiO2 < 50%, lactate level < 3 mmol/l and urine output > 1 ml/kg/h [23]. A follow-up randomized controlled trial study from China recently demonstrated that timing of thoracoscopy performed within 85 h of birth for left-sided defects—‘mild to moderate CDH’ resulted in comparable perioperative morbidities (%) with early surgical operation (24–48 h) [24]. Tan et al. [10] proposed that in the first 72 h after birth cardiopulmonary physiology status is too labile to best predict optimal timing for surgery and thereafter suggested a preoperative OI less than 3 may offer better objective stability of PH. In our current study we found CDH newborns who underwent surgery achieved their lowest pre-op OI at 4.5 ± 5.5 on day 6 (5.8 ± 5.4 days) following delivery. A higher OI and age at operation was noted in CDH patients who received HFOV treatment as we have discussed earlier (Table 2).

A 34.5% (19/55) pre-operative case mortality rate was observed in our CDH study population with a significanly higher OI at 24h, 48h and 72 h (Table 3). Surgical repair was undertaken in 36/55 (65.4%) index cases. Type A CDH defect were noted in 75% cases, type B in 19.4% and type C in 5.6% patients. However our findings perhaps given the study size population did not show the grade severity classification of CDH defect to significantly influence mortality (%)—(P = 0.148). Post-operative deaths after CDH repair were recorded in 3/36 (8.3%) patients which were contributed to by neonatal sepsis—(two cases unrelated to PPHN) and one single immediate post-operative fatality exacerbated by PPHN. We found no differences here in the pre-operative OI between these two CDH groups—(14.5 ± 12.9 in post-operative mortality CDH cohort vs 3.8 ± 3.5 CDH survival group; P = 0.20). Due to the very low number of post-operative deaths recorded we are thus unable to identify significant differences of OI in this specific small group of operated patients.