Comprehensive newborn screening program: ARAMCO experience, the national need and recommendations.

Comprehensive screening programs for congenital diseases of newborn infants are lacking at a national or regional level. A comprehensive newborn screening program modified to the needs and resources available was established in ARAMCO Dhahran Health Center. This program includes screening for congenital hypothyroidism, phenylketonuria, abnormal hemoglobins, glucose-6-phosphate dehydrogenase deficienc, and blood group incompatibilities. Several problems were encountered during the operation which required several modifications of the program. The organization and procedures of the program are described. Since the program was started in 1980, more than 70,000 newborn infants have been screened. Valuable epidemiological data have been collected and necessary information for direct clinical use was obtained. A national program to screen all neonates in the Kingdom of Saudi Arabia is achievable and urgently needed. Recommendations based on ARAMCO experience are given.

Conjoined twins: medical, surgical and ethical challenges.

Four sets of conjoined twins were reviewed. One set was of the omphalopagus type with no associated abnormalities and were successfully separated at 12 days of age. The other three were of the thoracoomphalopagus type with major cardiac and other abnormalities, they were not amenable to surgery and did not survive. Conjoined twins require precise clinical and radiological evaluation. Many factors contribute to the management of such twins and ethical issues must be considered before surgical separation is undertaken.

Treatment of severe persistent pulmonary hypertension of the newborn with magnesium sulphate.

Eight of nine newborn infants with severe persistent pulmonary hypertension of the newborn (PPHN), and a predicted mortality of 100%, and one infant with a predicted mortality greater than 94% based on alveolar-arterial oxygen tension difference [A-a)DO2) were treated with magnesium sulphate (MgSO4) as a life saving therapy after they failed to improve with conventional treatment. Magnesium at high serum concentrations decreases pulmonary pressures and is a muscle relaxant and sedative. Diluted MgSO4.7H2O solution (200 mg/kg) was given intravenously over 20-30 minutes. No changes in the treatment were made after MgSO4. Mean serum magnesium concentration was maintained between 2.88 and 5.67 mmol/l by continuous intravenous infusion (six infants). Baseline arterial oxygen tension (PaO2) and haemoglobin oxygen saturation had mean (SD) values of 4.66 (1.8) kPa and 60.4 (29.7)% respectively, which started to increase one hour after MgSO4 infusion, and increased significantly at six hours to 12.04 (7.07) kPa and 91.8 (10.88)% respectively. Arterial carbon dioxide tension (PaCO2) decreased and pH increased significantly after one hour compared with the baseline value. PaO2 increases are probably secondary to a decrease in pulmonary vascular resistance and pressure, decrease in a right to left shunt, better ventilation:perfusion ratio, and PaCO2 decrease and pH rise. Seven infants survived (77.8%). These results demonstrate the beneficial effect of magnesium in the management of PPHN when other accepted treatment fails, is contraindicated, or not available.

Screening for glucose-6-phosphate dehydrogenase deficiency can prevent severe neonatal jaundice.

Infants with the severe variant of glucose-6-phosphate dehydrogenase (G6PD) deficiency may develop hyperbilirubinaemia sufficiently severe to cause kernicterus and death, acute haemolysis on exposure to oxidant stress, congenital non-spherocytic haemolytic anaemia and, rarely, increased susceptibility to bacterial infection. In spite of these potential problems, G6PD deficiency is often not included among screening programmes for inherited disorders. In a comprehensive screening and educational programme, we tested around 34,000 infants for G6PD deficiency. Of the total group, 18.4% (24.5% boys and 11.8% girls) were deficient. Forty-two of the 6246 (0.67%) G6PD-deficient infants required exchange transfusion. None of them developed kernicterus. By contrast, of 4755 infants who had not been screened because they were born at home, three developed kernicterus. In addition, four G6PD-deficient infants had developed kernicterus in the 20-month period prior to the screening programme. None of the hyperbilirubinaemic infants had blood group incompatibility or any other identifiable cause of hyperbilirubinaemia. To avoid this disastrous result, we believe that neonatal screening for G6PD deficiency, together with a comprehensive education programme, is advisable in those parts of the world where the severe variant of G6PD deficiency is prevalent.

Discordant anencephaly with a cleft lip and palate in a pergonal-induced triplet pregnancy.

Anencephaly in triplets and pergonal induced pregnancies is a very rare incident. Associated cleft lip and palate has never been reported in these case. In this paper we report the first case of an anencephalic infant with cleft lip and palate in a set of pergonal-induced discordant triplet pregnancy.

A new syndrome of congenital hypoparathyroidism, severe growth failure, and dysmorphic features.

Twelve infants (six boys, six girls) with severe hypocalcaemic tetany or convulsions were seen over a three year period. Nine patients were symptomatic in the newborn period. Their hypocalcaemia was associated with hyperphosphataemia and very low concentrations of immunoreactive parathyroid hormone. None of the babies suffered from congenital cardiac disease. Cell mediated immunity, measured in five patients, was normal. There were no chromosomal abnormalities but all patients shared several dysmorphic features including deep set eyes, microcephaly, thin lips, beaked nose tip, external ear anomalies, micrognathia, and depressed nasal bridge. Mental retardation of varying degree was found in all patients. All had severe intrauterine and postnatal growth retardation. Four patients have died. The remaining eight patients are on treatments with vitamin D and calcium supplements with no change in their growth pattern. We believe that this association of congenital hypoparathyroidism with severe growth failure and dysmorphism represents a new syndrome.

Complications of diazoxide treatment in persistent neonatal hyperinsulinism.

Seven infants with persistent neonatal hyperinsulinism were treated in Dhahran Health Centre from 1983 to 1986. The insulin:glucose ratio (serum insulin concentration pmol/l) divided by the blood glucose concentration (mmol/l) ranged from 12 to 636, mean (SD) 177 (201). To control hypoglycaemia, diazoxide (12-24 mg/kg/day) was given in a continuous intravenous glucose infusion (12-22 mg/kg/min) on 11 separate occasions, four infants twice each and three infants once each. An increase of more than one standard deviation in the heart and respiratory rates, together with other symptoms of heart failure, was considered to be evidence of diazoxide toxicity. Cardiorespiratory failure (toxicity) occurred on eight of the 11 occasions (73%) in seven infants. The average daily fluid intake, weight change, respiratory rate and heart rate before treatment were similar whether or not the infant developed toxicity. A diazoxide toxicity index was obtained by multiplying the dose of diazoxide by the insulin:glucose ratio to relate the diazoxide dose to the severity of the disease. In all instances when the toxicity index was more than 1533 (mean (SD) 3732 (2741) cardiac toxicity developed. In contrast, infants with a toxicity index of less than 675 (mean (SD) 364 (270), had no symptoms of toxicity. Symptoms were significantly related to the severity of the disease and the diazoxide dose. It is possible to use the toxicity index to predict the risk of toxicity and to calculate a safe dose of diazoxide in infants with persistent neonatal hyperinsulinism.

Incidence and causes of sepsis in glucose-6-phosphate dehydrogenase-deficient newborn infants.

To determine the susceptibility to sepsis in newborn infants deficient in glucose-6-phosphate dehydrogenase (G6PD), we screened 33,943 Saudi Arab infants. Deficiency of G6PD was found in 18%. Sepsis was determined by the presence of clinical signs of sepsis and confirmed by positive blood cultures. Sepsis was documented in 75 infants (2.2/1000). The incidence of sepsis was significantly higher in 6138 G6PD-deficient infants (3.4/1000) than in the 27,805 with normal G6PD activity (1.9/1000; p less than 0.02). The incidence of catalase-positive organism sepsis was higher in G6PD-deficient infants (2.9/1000) compared with those with normal G6PD activity (1/1000; p less than 0.0002), whereas the incidence of catalase-negative organism sepsis did not differ (p less than 0.2). Deficiency of G6PD was more common in infants with late sepsis (46%) than in those with early sepsis (21%) and in all infants screened (18%) (p less than 0.03 and p less than 0.001, respectively). We conclude that neonates with G6PD deficiency are more susceptible to late sepsis and to infection with catalase-positive organisms. The exact mechanism for the increased susceptibility is not clear, but a partial explanation could be lack of leukocyte bactericidal activity associated with G6PD deficiency, and an increased susceptibility to infection caused by hyperferremia resulting from lysis of G6PD-deficient erythrocytes.

Persistent neonatal hyperinsulinism.

Over a 3-year period, the diagnosis of persistent neonatal hyperinsulinism (PNH) was made in seven infants, from an unselected cohort of 18,726 births, all of Saudi Arabian origin. Thus the incidence of PNH was one in 2,675 births. The high incidence, associated consanguinity, and occurrence in siblings suggest that PNH may be inherited as an autosomal recessive disorder.

Infantile-onset arthritis and multisystem inflammatory disease: "a new syndrome".

A case is presented with early-onset polyarthritis involving both large and small joints, prolonged fever, skin rash, hepatosplenomegaly, persistent cerebro-spinal fluid pleocytosis, brain atrophy, macrocephaly with ventricular dilatation, a persistently open fontanelle, lymphadenopathy, subcutaneous nodules, developmental delay, failure to thrive, persistent hypochromic microcytic anemia, leukocytosis with shift to the left, early thrombocytopenia followed by thrombocytosis, high erythrocyte sedimentation rate, elevated immunoglobulin level, and vasculitis involving several organs. Thirteen cases have been previously reported under different names. A unified name is needed; we suggest "infantile-onset arthritis and multisystem inflammatory disease."

Regulation of upper airway maintaining muscles during progressive asphyxia.

The electromyographic activity of an upper airway muscle (genioglossus, GG) and the diaphragm were studied in 10 adult and three young anesthetized rabbits during progressive asphyxia induced by airway occlusion. Results were similar for both age groups. Peak inspiratory activity of GG muscle increased more than that of the diaphragm during both the hyperpnea and gasping (P less than 0.05). The increase in GG activity during gasping was not significantly different from that during hyperpnea even though an important stimulus, arousal, was absent during gasping. During end stage asphyxia, as the strength of gasps grew weaker, the rate of loss of GG muscle activity was greater than that of the diaphragm. However, GG activity remained greater than that of the diaphragm at the time of the last spontaneous gasp. As asphyxia progressed, inspiratory duration and the inspiratory contour of integrated electromyogram activity of both muscles changed. These data indicate differences in the control mechanism of the genioglossus and diaphragm during acute severe asphyxia. Increased upper airway muscle activity seen during gasping should help preserve upper airway patency and facilitate autoresuscitation by gasping. These observations of coordinated changes in timing and activity of two functionally different respiratory muscles support the concept that gasping is a highly organized function of the respiratory centers.

Influence of upper airway pressure changes on respiratory frequency.

Influences of pressure changes within the upper airway on respiratory frequency were studied in anesthetized rabbits. These reflex effects were investigated in two ways: (1) by applying sustained negative or positive pressures to isolated upper airway in vagally intact animals during tracheostomy breathing, and (2) by briefly occluding the nasal airways of vagotomized animals at end expiration. Negative pressure applied to isolated upper airway decreased the respiratory frequency (P less than 0.01). Decrease in respiratory frequency correlated with magnitude of pressure change. In contrast, positive pressures produced an increase in respiratory frequency (P less than 0.05). But, the increase in frequency correlated poorly with magnitude of positive pressure change. A post-stimulus effect lasting several breaths was seen following the release of both negative and positive pressures (P less than 0.01). Nasal occlusion in vagotomized animals was associated with an increase in Ti and Ttot of the first nasally occluded breath (P less than 0.05). Increase in Ti was not associated with an increase in peak diaphragmatic activity. This would result in decreased inspiratory load on the upper airway patency maintaining muscles by reducing the mean inspiratory pressure. Hence, these reflex responses to airway pressure could play a functional role in the maintenance of upper airway patency.

Breathing pattern and transcutaneous oxygen tension during motor activity in preterm infants.

We studied breathing pattern and transcutaneous oxygen tension (TcPO2) during episodes of sustained generalized motor activity in 18 hospitalized preterm infants. We used a newly developed quantitative method for assessing minute ventilation in infants during vigorous motor activity. We recorded respiratory air flow, tidal volume, esophageal pressure, TcPO2, and electromyograms of various muscle groups. We observed a distinctive pattern of breathing ("exertional breathing pattern") that was invariably associated with episodes of "squirming" motor activity. This breathing pattern is characterized by reduced minute volume, intermittent Valsalva maneuvers, and obstructed inspiratory effects (obstructive apnea). Episodes of squirming with the accompanying altered breathing pattern were usually followed by a decrease in TcPO2. These episodes occurred spontaneously or could be induced by sensory stimulation. They appear to be a significant cause of obstructive apnea and TcPO2 instability in hospitalized preterm infants, and were responsible for 30% of sudden decreases in TcP[O2 of 10 mmHg or greater.

Genioglossus muscle responses to upper airway pressure changes: afferent pathways.

The afferent pathway of an upper airway reflex in which genioglossus muscle electromyographic (GG EMG) activity is influenced by pharyngeal pressure changes was investigated in 20 anesthetized rabbits. We took advantage of the fact that the upper airway was separated into two compartments by pharyngeal closure occurring when the animals breathe through a tracheostomy. This allowed pressure to be delivered selectively either to the nose and nasopharynx or to the larynx and hypopharynx. Midcervical vagotomy did not eliminate the GG EMG response to pressure stimuli. On the other hand high cervical vagotomy or superior laryngeal nerve section eliminated the response in the laryngeal compartment, but not in the nasopharyngeal compartment. Topical anesthesia of the mucosa of the nose, pharynx, and larynx abolished the response in both compartments. Therefore we conclude that more than one afferent pathway exists for this upper airway pressure reflex; the primary afferent pathway from the laryngeal compartment is the superior laryngeal branch of the vagus nerve, whereas the primary afferent pathway for the nasopharynx is nonvagal. Trigeminal nerve, glossopharyngeal nerve, and/or nervus intermedius carry nonvagal afferents from the nasopharynx and nose. The topical anesthetic and nerve section studies suggest that superficial receptors mediate this response. The occurrence of swallowing in response to upper airway pressure changes and its elimination by topical anesthesia or superior mechanoreceptors may mediate both genioglossus respiratory responses and swallowing responses.

Influence of upper airway pressure changes on genioglossus muscle respiratory activity.

The effects of change in pharyngeal airway pressure on electromyographic (EMG) activity of a pharyngeal dilating muscle (genioglossus) were investigated in 20 anesthetized rabbits. In vagotomized animals, upper airway loading maneuvers (nasal occlusion) increased the peak inspiratory activity of the genioglossus (GG) muscle on the first occluded breath. In contrast, "unloading" maneuvers (switching from nose to tracheostomy breathing) decreased GG activity. To further characterize the GG response, sustained pressure changes were produced within the isolated upper airway. Negative pressure increased GG activity; positive pressure decreased it. A poststimulus effect consisting of increased GG activity compared with control was seen following both negative- and positive-pressure stimuli. Cyclical pressure changes applied to the isolated upper airway increased the GG activity. These observations indicate the presence of reflex pathways that regulate GG muscle activity in response to upper airway pressure loads. This reflex system appears to play a role in regulating GG activity during tidal breathing and could be important in ensuring pharyngeal airway patency.