Treatment of hypertension
The selection of an appropriate hypotensive drug for the preterm and neonate with nt poses many problems and uncertainties. The dilemmas arise from the need to carefully assess the benefits and harms of both the potential for the development of organ complications in the case of untreated nt and the potential for side effects of the drug used. The general principle of hypotensive therapy in this age group boils down to initiating treatment under strictly defined circumstances, having first eliminated iatrogenic causes of elevated blood pressure (pain, inotropic drugs, conductivity).

The safest treatment is intravenous administration of short-acting drugs (Table 6). In this way, the best control of blood pressure can be achieved, as well as reducing the risk of sudden uncontrolled hypotension that can consequently lead to CNS blood supply disorders, especially in neonates born prematurely, in whom the mechanisms of autoregulation of cerebral flow are not yet fully developed. Although the safest form of drug delivery is slow intravenous infusion, bolus drug delivery appears to be effective and justified in some neonates. Oral hypotensive therapy is reserved for neonates in good general condition and previously treated with intravenous drugs (Table 7).

Due to the lack of long-term randomised trials evaluating the efficacy of hypotensive treatment in the youngest age group, most expert recommendations are based on clinical observations. According to these recommendations, treatment should not be initiated in an asymptomatic newborn with blood pressure values between the 95th and 99th percentile. Feld and Waz recommend initiating hypotensive treatment when blood pressure values are found to be above the 99th centile or when organ complications occur with blood pressures above the 95th centile. However, there are no doubts regarding the immediate initiation of treatment for severe hypertension exceeding the expected values for a given age by 30%. While in older children the guidelines in Task Force Report 4 and the recommendations of the European Society of Hypertension have clearly defined the indications for starting antihypertensive treatment (second degree hypertension, symptomatic hypertension, presence of organ damage), these recommendations do not work well in the youngest age groups. This is due to the difficulty of classifying the severity of hypertension in neonates, as well as the difficulty of assessing baseline markers of organ damage (see above).

An additional problem of hypotensive therapy in neonates remains the fact that many hypotensive drugs that are in common use in adults are not registered for the youngest age groups, and there are few reports of their efficacy in the youngest. The general rule of thumb for pharmacotherapy in neonates and infants boils down to the selection of the drug according to the potential aetiology of nt and concomitant disorders, and treatment is started with the lowest possible doses of the drug.

Diuretics for the treatment of newborn nt are of limited use, which is limited to conditions with conductivity. Loop diuretics (furosemide) used in gradually titrated doses are the drugs of choice in hyponatraemia-hypertension syndrome. In other situations, especially in combination with other drugs, they may cause uncontrolled hypotension.
Beta-blockers, among them propranolol, show great benefit and relatively few side effects. However, due to the additional alpha-receptor blocking effect and the possibility of intravenous delivery, labetalol appears to be a much better alternative.
Studies by Flynn, and other authors, have shown the effectiveness of intravenous calcium channel blocker therapy in this age group. Among these, nicardipine is the most commonly used , and among the drugs in oral form, nifedipine and amlodipine. As these drugs strongly relax the vascular musculature and reduce peripheral resistance, they offer the potential to abolish autoregulation of cerebral flow and increase CNS and gastrointestinal bleeding. It is important to bear in mind the rapid and unpredictable effect of nifedipine administered in drop form, which should not be used in this form. Therefore, oral forms of amlodipine are now increasingly used.

There are also reports on the efficacy of esmolol, labetalol and sodium nitroprusside.

Among the drugs that block the renin-angiotensin-aldosterone system (RASS), the most common uses are captopril used orally, and intravenous enalaprilat. However, when using converting enzyme inhibitors, care must be taken to be aware of the possibility of inducing difficult-to-control hypotension, particularly with intravenous delivery. Captopril, however, is the only oral renin system blocker approved for use in neonates. Thus, it has a primary use in cases of severe renin-dependent nt, e.g. in unilateral renal artery stenosis when the target treatment is nephrectomy, in patients with aortic coarctation in the postoperative period, and in children with renal-dependent nt. An additional major problem in the wider use of RASS blocking drugs is the relatively small amount of data on the effect of RASS blockade in neonates and preterm infants on maturation and renal function. The isolated reports although proving the hypotensive efficacy of this drug group, but at the same time the potential for disruption of postnatal renal maturation, appear to be of concern. According to expert opinion, converting enzyme inhibitors, if possible, should not be used until the 44th week of postconceptional age. Another described complication of converting enzyme inhibitors is acute renal failure, especially after intravenous administration of enalaprilat. This is related, on the one hand, to the dependence of renal flow in the neonate and preterm infant on RASS and, on the other hand, to the effect of RASS on renal maturation.

As nt in neonates is secondary, surgical treatment is important. This applies to nt caused by renal and abdominal tumours as well as vascular pathologies. In the case of coarctation of the aorta and mid-aortic syndrome, reconstructive procedures, both surgical and percutaneous vasodilatation, are of primary importance. In the treatment of nt in renal vein thrombosis leading to renal necrosis, normotension can generally be achieved with ad hoc pharmacological treatment, while if nt persists, nephrectomy is the definitive treatment. Due to the small diameter of the vessels, nephrectomy is also the most common treatment for nt caused by renal artery stenosis.

Evaluation of the effectiveness of hypotensive treatment

Due to the relatively high risk of adverse effects of hypotensive pharmacotherapy in neonates, as well as the risk of acute or distant complications resulting from delayed treatment, clearly defined assessment points should be used when initiating hypotensive treatment and evaluating its efficacy. As in older children, criteria for treatment efficacy include the hypotensive effect, regression of organ damage, resolution of the underlying cause of nt, and the consequent achievement of normotension with the possibility of discontinuing hypotensive drugs. Data provided by Peterson et al. show that neonates with nt who are started on hypotensive treatment and causal treatment (generally surgery) experience regression of organ damage relatively quickly. Among neonates with hypertensive cardiomyopathy who received either causal treatment or effective hypotensive treatment, normalisation of left ventricular function was seen in 62-100% of patients as early as 8-9 days of treatment.

Prognosis

As causal (surgical) treatment is possible in the majority of cases of neonatal nt, the short-term prognosis in this group of patients is usually good and depends on the main diagnosis. Only in a limited number of cases, nt may persist into later life and require ongoing hypotensive treatment. These include, for example, cases of nt in the course of coarctation of the aorta, in which even early surgical treatment does not fully prevent the risk of nt manifesting in later life, and congenital malformations of the urinary tract, in which nephron mass is reduced and chronic kidney disease may develop years later. Another burden causing the risk of developing nt in the future are complications of prematurity and intrauterine dystrophy associated with congenital reduced nephron mass, an effect of perinatal programming and rapid weight gain.