Object-oriented Life Cycle Assessment Application

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Many studies reported male preponderance among babies with seizures.5-9, 11-14 This is in keeping with male to female ratio of 2.9:1 reported in the present study. The reason for this is unknown.

It may however be partly related to the other factors in the male infant. For example, male infants have increased susceptibility to infections including meningitis which may manifest as seizures. In the present study neonatal infection was more common in neonates with seizures. Female infants in contrast to males are believed to be relatively protected by immunoglobulins elaborated by gene loci coded on X-chromosomes. Since females have two X-chromosomes they are believed to have more gene loci that code for more immunoglobulins hence are more protected from infections than males.⁸¹

There was higher proportion of term babies with seizures compared to those without seizures in the present study. This was similar to the observations by other workers within^12-14 and outside Nigeria.

5-9 This might be related to the fact that term babies are admitted to the hospital because they are ill, unlike preterm babies who are often admitted solely because they are delivered before term. Also term babies having more developed musculatures and better neuronal myelination are more likely to present with clinically observed seizure activities. Since seizures were defined in the present study based only on clinical identification, the finding of more term than preterm babies with seizures was not unexpected.

The seizure type that was predominantly observed in the present study was generalised tonic seizures which accounted for over 40.0% of the seizure types. This was in agreement with the findings of Holden et al,⁸² but are different from those of Omene et al¹¹ who reported clonic type as the most common seizure type. The difference may be related to the difference in the methods of seizure classification. While Volpe method of classifying neonatal seizure was used in the present study and that of Holden et al, Omene et al did not apply the Volpe method of classifying neonatal seizures, they just classified seizures as clonic, tonic or subtle types. The type of seizures however was not found to be related to outcome in the present study as previously reported in other studies.^56,82

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Also of note was the higher proportion of teenage mothers whose infants had seizures. This finding corroborates the report by Ogunniyi et al⁷⁸ at Ile-Ife. Teenage girls who are often unmarried and poorly supported have been reported to have increased risks of adverse perinatal events like prolonged obstructed labour and eclampsia which predispose to neonatal asphyxia and seizures.^{66, 78, 79} In addition, late presentation of the ill infant of the teenage mother to the hospital may also explain the higher proportion of their infants having seizures compared to infants of older and more experienced mothers.^{78, 79}

Women from low socio-economic class were found in the present study to more likely have babies with clinical seizures compared to those from high socio-economic class. Women from low social class are usually unable to afford and or access quality obstetric care as they are often required to pay

‘out of pocket’ for these services; with attendant poor obstetric and perinatal care.^23,24,80 They also tend to have little or no formal education, hence they are more likely to patronize alternative, unorthodox or sub-standard obstetric care in mission homes, private set-up and from traditional birth attendants. This may lead to increased maternal and neonatal mortality and morbidity, including neonatal seizures.^{80, 84}

Babies delivered outside the hospital setting particularly in mission houses and private maternity homes were found to be significantly more likely to have seizures. This is in keeping with similar reports by Ogunlesi et al¹⁴ in Sagamu and Adebami¹⁷ in Osogbo, Nigeria and Mwaniki et al²⁶ in Killifi, Kenya where a large proportion of the babies reported with clinical seizures in their studies were delivered outside the hospital. Delivery outside the hospital setting predisposes to increase maternal and or newborn morbidity and mortality because such deliveries are often conducted by unskilled personnel who may not appreciate danger signs and need to refer the parturient to higher health facilities.^23-25 Such deliveries are often complicated by prolonged and or obstructed labour and eclampsia.²⁵ As a consequence, these complications were found to be significantly associated with

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clinical seizures in the present study. This finding was in keeping with reports by Omole-Ohonsi et al⁸⁵ from a tertiary centre in Kano, Nigeria where prolonged obstructed labour was found to increase neonatal morbidity, including predisposition to hypoxic–ischaemic injuries and subsequently early onset seizures.⁸⁵ Prolonged obstructed labour causes intrapartum hypoxaemia, acidosis, meconium stained amniotic fluid as well as abnormalities in cardiotographic tracings.^27-28 These cause intrapartum asphyxia and subsequent hypoxic-ischaemic (asphyxial) encephalopathy which often manifest as neonatal seizures.^27,28

Antepartun eclampsia has been widely reported especially from developing countries to be associated with poor perinatal outcome.^86-88 Antepartun eclampsia puts the life of the foetus in jeopardy as there is usually associated utero-placental circulation compromise, leading to intrauterine hypoxaemia and ischaemia.⁸⁶ Studies from Pakistan^86,87 observed that infants of mothers with pre-eclampsia and pre-eclampsia are at increased risk of operative deliveries resulting in low APGAR score, with the need for endotracheal and intubation neonatal intensive care. There is an associated neonatal morbidity including seizures.^86-87 Infants of mothers with eclampsia are not only affected by complications associated with eclampsia, they also suffer from the respiratory depressant effects of the various anticonvulsants employed in the management of such mothers.⁸⁷

The aetiological factors found in the present study that were associated with early- onset clinical seizures in the newborn included birth asphyxia, and its neurologic complications such as cerebral oedema, transient metabolic disorders like hypocalcaemia and hypoglycaemia. Intracranial bleeds, meningitis and kernicterus predominated among babies with late-onset seizures. These observed aetiological factors were similarly reported by previous workers.11-14, 19, 20 This implies that early-onset neonatal seizures should arouse the suspicion of these diagnoses; and management of babies with early-onset seizures should commence along the line.

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There was no identified aetiological factor in about 10.0 percent of babies with clinical seizures in the present study. This was within the range of 5.0-10.0% previously reported in other studies.^5-7,14 The availability of imaging facilities like MRI and CT scans coupled with facilities for viral studies would have helped to further identify the aetiological factors of newborn seizures in the present study and hence more appropriate management of the babies with seizures.

Birth asphyxia causing hypoxic-ischaemic encephalopathy has been reported to be a leading cause of neonatal seizures in resource-poor regions of the world.11-14, 17, 26 It is common in areas with poor obstetric and neonatal care, including Nigeria. In the present study 61.0% of the babies with seizures had birth asphyxia. This was in keeping with prevalence of 62.7% and 60.3% among babies with seizures reported by Adebami¹⁷ in Osogbo and Ogunlesi et al¹⁴ in Sagamu respectively. The prevalence of birth asphyxia as an aetiological factor in neonatal seizures observed in the present study was much higher than the 36.5% reported by Moayedi et al⁸⁹ in a retrospective study from a large general hospital in Iran, as well as 21.0% reported by Mwaniki et al²⁶ from a hospital in rural Kenya.This might be due to the fact that the previous studies from Nigeria like the present study were conducted in tertiary centres where complicated cases and very sick newborns are referred to; hence more likely to present with babies the higher prevalence of asphyxia and seizures. Babies with asphyxia should therefore be closely monitored, and assessed for metabolic and other complications to forestall the development of seizures and consequent poor outcome.

Hypocalcaemia was observed in 62.5% of the babies with seizures in the present study. This was in keeping with the prevalence of 63.0% reported by Ogunlesi et al.¹⁴ The prevalence of hypocalcaemia among babies with clinical seizures reported in the present study and other studies from Nigeria was high compared to observations by Numes et al⁴ from Brazil who reported a prevalence of 10.0% and equally low prevalence of 7.4% among cohort of babies with clinical seizures from Kenya.²⁶ Mothers in

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Nigeria have been documented to have relatively low serum calcium level, and this has also been shown to put babies of such mothers at increased risk of neonatal hypocalcaemia.⁴⁴

Hypomagnesaemia was observed in 32.7% of babies with clinical seizures. It is usually found occurring together with hypocalcaemia and may both be associated with perinatal asphyxia.^42,43 The mean serum magnesium as found in the present study was similar between babies with seizures and those without seizures. So also was the prevalence of hypomagnesaemia between these two groups as the slight difference between them was not significant. This would suggest that hypomagnesaemia may not be an important aetiological factor of neonatal seizures in the study location. More studies are however needed to ascertain the role or contributions of hypomagnesaemia to seizures in the newborn.

Hypoglycaemia was observed in 27.3% of the babies with clinically identifiable seizures in the present study. This finding agreed with the prevalence of 26.5% reported among neonates with seizures by Moayedi et al⁸⁹ in 2007 from Iran. However, there was no difference found in the present study between the proportions of babies with hypoglycaemia who had clinical seizures compared to those without seizures. This might due to the fact that there were many neonatal conditions that could predispose the sick infants to hypoglycaemia which may not necessarily manifest as clinical seizures.⁴¹ Since brain damage and neurologic deficit could occur even in infants with asymptomatic persistent hypoglycaemia, prompt correction of hypoglycaemia even without clinical symptoms is advocated.⁴¹

Anaemia was observed in 34.5% of the babies with clinical seizures, and was significantly associated with seizures. The association between anaemia and neonatal seizures was in agreement with the report from Sagamu.¹⁴ Anaemia causes hypoxaemia which may cause or contribute to neonatal encephalopathy manifesting as seizures.² This implies that anaemia should be specifically sought for in

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very ill newborns and if present promptly corrected to reduce the occurrence of seizures in such babies and this may improve the outcome.

Cerebral oedema diagnosed using transfontanelle ultrasonography was found in 21.3% of the babies with clinical seizures in the present study and all the babies had features in keeping with perinatal asphyxia. This finding was higher than the prevalence of 14.8% of cerebral oedema reported among babies with perinatal asphyxia by Meek et al⁹⁰ in London.

Cerebral oedema usually results from cellular damage from hypoxic-ischaemic injuries (cytotoxic) and associated injurious cascade activation. Magnetic resonant imaging (MRI) and computerised tomography (CT) scans are preferred diagnostic modalities in babies with hypoxic injuries and encephalopathy.⁹¹ Nevertheless, in resource-poor regions cranial ultrasound are still useful, particularly as it is more easily available, accessible and affordable than the sophisticated MRI and CT scans in low-income countries.^92,93 Hence the routine use of transfontanelle ultrasound in the investigation of infants with seizures may be worthwhile in resource-poor centres. There is still paucity of data on the role of ultrasound in the diagnosis of cerebral lesions among sick neonates in Nigeria and other developing countries.^92-94

The prevalence of 7.7% of intracranial haemorrhage diagnosed with cranial ultrasound among babies with clinical seizures in the present study was similar to 6.0% reported in England by Mercuri et al⁹⁵ alsousing transfontanelle ultrasound. It was however much less than 26.0% reported by Looney et al⁹⁶ in a review of asymptomatic neonates assessed by Magnetic Resonance Imaging (MRI). Variation in the prevalence of intracranial haemorrhages has been reported to be influenced by the cohort of babies studied, sensitivities and timing of the diagnostic imaging used and expertise of the personnel interpreting the results.⁹⁴

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The independent predictors of clinical seizures among admitted neonates found in the present study were male sex, low socio-economic status, term gestation, delivery outside the hospital and anaemia. This was in keeping with the finding of Saliba et al⁸ in a population-based study in Harris County where like the present study, male gender, young maternal age and delivery in private hospitals were the predisposing factors to seizures in their newborns. Apart from the male sex which is not modifiable, the other risk factors are largely modifiable and preventable.

Among babies with seizures, the risk factors for mortality observed in the present study included cerebral oedema, co-existence of birth asphyxia and hyponatraemia and occurence of clinical seizures in the first 24 hour of life. The occurrence of clinical seizures within 24 hours of delivery is a pointer to adverse perinatal events usually from delivery not attended to at all or attended to by unskilled personnel often outside the hospital.²³ Patronage of home delivery or delivery outside the health facilities may be informed by poverty, ignorance, religious and cultural beliefs as observed by Adelaja et al,²³ which support the finding in the present study that low socio-economic status was a risk factor for mortality among babies with clinical seizures.

Coexistence of asphyxia with hyponatremia was observed in the present study to be a risk factor for mortality among babies with clinical seizures. Coexistence of metabolic problems with asphyxia was also observed by Ogunlesi et alin Sagamu.¹⁴ The presence of hyponatraemia in babies with asphyxia may be a sequelea of syndrome of inappropriate anti-diuretic hormone secretion which is a recognized complication of perinatal asphyxia.^3,27 It may also due to failure of the ATPase-dependent membrane Na⁺/K⁺ pump (sick cell syndrome) leading to net influx of sodium and water intracellularly and cellular damage and death,¹⁸ hence the poorer prognosis observed among this group of babies. This implies that newborn admitted with seizures should be closely monitored for cerebral oedema and electrolyte derangement particularly serum sodium, in other to improve their chances of survival.

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Newborns with clinical seizures in the present study were four times more likely to die compared to those without seizures. In addition, clinically identifiable neonatal seizures contributed to more than 40.0% of the overall neonatal mortality observed during the study period. The significant contribution of seizures to neonatal morbidity and mortality has also been reported by other workers in Nigeria^11-14,17 and outside the country.^5-10 These findings were comparable to a mortality rate of 25.0%

observed by Numes et al in Brasil⁴ which like the present study was 3-4 times more than those without seizures. Higher mortality rates of 43.8% and 43.6% were however reported from Osogbo¹⁷ and Sagamu respectively.¹⁴ Mortality rates are dependent on the nature and severity of underlying aetiologies hence the variations reported mortality rates across centres.

Clinically identifiable newborn seizures are in no doubt ominous conditions that require early diagnosis, prompt search and management of the aetiological factors to improve survival, and reduce long-term sequelae which are often observed in such babies.

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