The newborn should receive human tetanus immunoglobulin (TIG) without delay [11,18]. TIG should be given as a single intramuscular (IM) dose of 500 U to bind the circulating toxin. However, the exact dose has not been determined, and total doses as high as 3,000-6,000 U are also recommended. Part of the dose can be infiltrated around the identified wound. If TIG is unavailable, equine tetanus antitoxin can be administered. When this antitoxin is given, immediate and delayed reactions to the antitoxin may take place. Although intravenous (IV) immunoglobulin offers passive immunization, there is insufficient familiarity with its dose and efficacy. Since tetanus itself does not confer an antibody response, those who underwent NT should be immunized with the series of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP), following complete recovery from the active illness [11,18].

Intrathecal administration of TIG or tetanus antitoxin enables higher concentration of TIG or antitoxin within the nervous system than IM administration. Despite the conflicting evidence on superiority of intrathecal over IM administration, a meta-analysis using 12 clinical trials involving 942 patients suggested that intrathecal administration is more beneficial than the latter [19]. A randomized controlled trial shows a reduced mortality in neonates who received intrathecal lyophilized human immunoglobulin while also receiving IM tetanus antitoxin [20].

C. tetani is susceptible to several antimicrobials: penicillins, cephalosporins, metronidazole, macrolides, tetracyclines, and imipenem [21-23]. It is recommended that specific antimicrobial therapy should be given with one of these modalities: per os or IV metronidazole (< 7 days of age, 15 mg/kg/day in divided doses; > 7 days, 30 mg/kg/day in divided doses, for 10-14 days); or IV penicillin G (100,000 U/kg/day administered at 6-hour intervals, for 10-14 days).

In the presence of an umbilical stump infection, it may be necessary to obtain the adequate antimicrobial coverage against polymicrobial aerobic-anaerobic pathogens [11]. Topical application of antimicrobials or disinfectants to the umbilical cord can serve as an effective preventive measure [16]. It is important to clean the wound by removing dirt, foreign object, and the dead tissue.

Clinical experience has demonstrated that mortality rate was lowest in those treated with combined therapy of diazepam, phenobarbital sodium, and/or chlorpromazine [21]. Omphalectomy has also been used to eliminate the toxin production [21].

Sedation and muscle relaxation in mild cases are achievable with diazepam. An initial dose of 0.1-0.2 mg/kg IV is given to release an acute spasm, followed by a continuous IV infusion of 15-40 mg/kg/day, titrated to control the spasm. After 5-7 days, it can be decreased by 5-10 mg/day and given orally or nasogastric [11].

Concomitant phenobarbital is given with a loading dose of 20 mg/kg and maintenance dose of 5 mg/kg/day to reach a serum phenobarbital concentration of 30-50 mg/dL. Substantial apnea occurs in about 10% of treated patients and respiratory support should be given immediately. Assisted ventilation is vital at higher doses. Other benzodiazepines, such as lorazepam and midazolam, are also acceptable. Further sedation with phenothiazines may be needed. If spasm cannot be suppressed, therapeutic paralysis is required [10].

Curariform agents, such as vecuronium, can induce neuromuscular blockade. Since these agents are often administered for extended period of time, the doses should be reduced slowly to prevent withdrawal symptoms [10].

Decreasing production of catecholamines can reduce the autonomic dysfunction. Labetalol (0.25-1.0 mg/min) that possesses both α- and β-blockade can be given. Providing only β-blockade (e.g., propranolol) is not advised because it may lead to sudden death [18]. Morphine sulfate (0.5-1.0 mg/kg/hour, continuous IV infusion) is frequently used to sedate and control the autonomic dysfunction by diminishing cardiac and vascular sympathetic tone. This drug adjusts cardiac instability without compromising [24]. Only magnesium sulfate has been evaluated in a randomized clinical trial of severe tetanus [25], and in several series for managing spasm including NT [26-29]. Thus, magnesium sulfate is given as a first-line agent in the management of NT. It relaxes the vascular smooth muscles and decreases catecholamine release from the adrenal medulla [30] and the adrenergic nerve endings [31]. Other medications to control the autonomic dysfunction are atropine, clonidine, and epidural bupivacaine [32,33].

Nutritional support is important, and should be provided early to satisfy the neonates’ high caloric and protein demands [34]. Enteral feeding is rarely utilized. Instead, a percutaneous endoscopic gastrostomy tube is frequently used in decreasing gastroesophageal reflux than a nasogastric tube. Central venous hyperalimentation may also be used. Heparins or other anticoagulants are given to prevent thromboembolism. Flotation bed or frequent position changes can prevent skin breakdown and peroneal nerve palsies [26,27].

Many survivors from NT experience developmental handicaps. Only a few studies evaluated the long-term effects of this entity. Furthermore, actual rates of sequelae are likely to be greater. A Kenyan study shows that 20%-40% of survivors sustained permanent brain damage, manifested as microcephaly, and neurological, developmental, and behavioral difficulties [35]. A Nigerian case series shows cerebral palsy, cognitive-developmental delay, and deafness in 20% of survivors [36]. These complications might have been caused by the hypoxia and hypoglycemia that are frequent throughout the illness.