Abstract

Background: Perinatal asphyxia is the third cause of neonatal death after prematurity and infection.

Objective: The purpose of this study was to determine the incidence, the etiology and the HIE score at the first day in term and near-term newborns with perinatal asphyxia at the University Hospital of Kinshasa.

Methods: 50 term and near-term neonates with perinatal asphyxia were studied prospectively after they were admitted in neonatal intensive care from November 2009 to January 2011. For each patient admitted the perinatal data were collected. Clinical assessment was performed by the Sarnat grading and the Thompson score within twenty-four hours. Medcalc® was used for statistics.

Results: 50 babies were scored. The median maternal age was 31 years. In 22% of the mothers preeclampsia was diagnosed. Urogenital infection, IUGR were other prenatal diagnoses. Median Apgar score was 4 after 1 minute, 5 after 5 minutes and 6 after 10 minutes. Sarnat grade 1 was seen in 16 patients, Sarnat grade 2 in 20 patients and grade 3 in 8. Thompson score in the first 24 hours was more than 7 in 60% of the patients. A good correlation was found between the Thompson score and the Sarnat grade (r: 0,77; p < 0,0001). 14 of the 50 babies died. Both Sarnat and Thompson score correlated significantly with mortality.

Conclusion: The incidence of perinatal asphyxia at the University Hospital of Kinshasa remains high and the majority of patients had a severe HIE.

Background

Perinatal asphyxia represents the third cause of neonatal death (23%) in the world after preterm birth (28%) and infections (26%) [1]. Hypoxic-ischemic encephalopathy (HIE) is the most frequent and important complication of perinatal asphyxia and the cause of 15–28% of all cases of cerebral palsy [2, 3]. The incidence of perinatal asphyxia is variable. In Sweden, Thornberg and Thiringer [4], in a region-based-study in Göteborg, reported perinatal asphyxia (Apgar score <7 at 5 min) in 5.4 per 1000 live births, and HIE was described in 1.8 per 1000 live births. Gonzales de Dios and Moya [5] reported in a hospital-based study in Spain, an incidence of perinatal asphyxia of 46.6 per 1000 live births, with an incidence of HIE of 1.19 cases per 1000 live births in 1996. Perinatal asphyxia was graded as non-severe (1-min Apgar score ≤6 and/or umbilical artery pH < 7.20, with abnormal fetal heart rate patterns and/or meconium-stained amniotic fluid, and the need for immediate resuscitation) and severe (1-min Apgar score ≤3 and umbilical artery pH < 7.10). Wayenberg et al. [6] observed in a multicentric study in Belgium, defining birth asphyxia by the presence of at least two of the three indicators (fetal distress, depression at birth and metabolic acidosis), an incidence of 15 per 1000 live births. The incidence of HIE was 5.9 per 1000 live term births. Actually the incidence of HIE due to perinatal asphyxia in developed countries is estimated at ∼1–6 per 1000 live term births [7, 8]. In Africa, Kinoti [9] in a multicentric study in maternity units in eight countries at the east and the south of Africa, and Cissé [10], in Mali have reported respectively an incidence of perinatal asphyxia of 229 per 1000 live births in 1993 and 67 to 132 per 1000 live births in 1996. Perinatal asphyxia was determined by an abnormally low Apgar score. In the Democratic Republic of Congo, different studies have been performed at the University Hospital of Kinshasa by Lubambu [11], Ngimbi [12] and Nkidiaka [13], reporting an incidence of perinatal asphyxia of 110, 29.8 and 39 per 1000 live births, respectively. Perinatal asphyxia in these studies was defined by a 1-min Apgar score <7, abnormal fetal heart rate and meconium-stained amniotic fluid. These studies have described neurological complications such as HIE, delay in the psychomotor development and a disturbed electroencephalogram (EEG) background, but no incidences were mentioned.

Perinatal asphyxia is sometimes unexpected, but often there are risk factors including antenatal factors such as hypertensive disorders, infections or bleeding; fetal causes like fetal growth restriction, breech presentation or chronic fetal distress; or intrapartum factors such as infections, placenta bleeding, uterine rupture, umbilical cord accidents or prolonged labor [7, 9, 14, 15]. Clinically, the Sarnat grade and the Thompson score are used to appreciate the severity of the HIE during the first 24 h after birth [16, 17]. The Sarnat 3 stage grading system of mild (grade 1), moderate (grade 2) and severe neonatal encephalopathy (grade 3) is based on clinical symptoms and EEG evaluation. The scoring system considers the responses of the neonate to handling, level of consciousness, changes in muscle tone and reflexes, presence of seizures and the duration of the symptoms within 7 days after birth. The Thompson score is a scoring system derived from the Sarnat grading and based on the neurologic examination and assessment of respiration and fontanel tension. The neurological components are tone, level of consciousness, fits, posture, Moro, grasp and suck. Each sign is scored from 0 to 3, and the score for each day is totaled. The higher the score, the more severely affected the infant. The maximum possible score is 22. The Thompson score is performed daily until normal or age 7 days. These clinical scores are performed to assess HIE, and a good relation with later neurodevelopmental outcome is described [6, 7, 16, 17].

Cooling is now the treatment of choice in the developed world and regarded as standard therapy in moderate to severe HIE (International Liaison Committee on Resuscitation [ILCOR] criteria). Although there are economic, cultural and prenatal factors that can be changed to decrease the incidence of perinatal asphyxia and HIE, the question raises whether this cooling technique should also be applied in DR Congo. To have a better estimate of the incidence and clinical picture of HIE in DR Congo, we performed a prospective observational study in 50 patients born with perinatal asphyxia.

Objective

The first objective of this study was to determine the incidence, the etiology and the HIE score at the first day in term and near-term newborns with perinatal asphyxia at the University Hospital of Kinshasa. The second objective was to describe the relation between the clinical HIE scores and the outcome (survival) of patients with perinatal asphyxia at discharge.

Methods

The University Hospital of Kinshasa is a tertiary hospital belonging to the University of Kinshasa, located in the west-southern part of Kinshasa, DR Congo. The hospital receives patients living in Kinshasa and patients referred from other regions of DR Congo. There are ∼720 deliveries annually at the University Hospital of Kinshasa. The neonatal unit counts 30 beds and admits infants born at the maternity of the University Hospital of Kinshasa, and 10–20% of the admissions are referred from the surrounding clinics.

Standard treatment applied in babies with perinatal asphyxia includes fluid restriction in the first 24 h (60 ml/kg/24 h), no oral feeding during the first 48 h and a vitamin K dosis. Phenobarbitone (10 mg/kg) is given when clinical convulsions occur. Oxygen is given by nasal cannula when respiratory distress is present. Patients cannot be ventilated or given continuous positive airway pressure (CPAP) in our setting. It is not possible to regulate fraction of inspired oxygen (FiO2); however, oxygen saturation is monitored, and the infant is given extra oxygen when oxygen saturation is <85%. Oxygen is weaned when the oxygen saturation is >90%. For each neonate, a blood sample is systematically taken on admission for hematology, biochemistry and bacteriology. The main parameters under supervision are respiratory rate, heart rate, temperature, oxygen saturation, urinary output, meconium emission and gastric residue.

We studied term and near-term neonates with perinatal asphyxia prospectively at the University Hospital of Kinshasa after they were admitted in the neonatal intensive care unit from November 2009 to January 2011. Perinatal asphyxia was defined if one of the following criteria were observed in the term or near-term infant (post-menstrual age of ≥36 weeks):

  • Apgar score <6 after 5 min

  • Resuscitation till 10 min after birth

  • The pH-value <7 and base excess >16 measured in umbilical cord blood or any blood sample (arterial, venous or capillary) within 60 min of birth.

Severe congenital malformations were excluded from the study.

Data were collected on all infants meeting entry criteria.

For each neonate admitted, we collected the data regarding pregnancy, delivery and neonatal admission. We reported, specifically, preeclampsia, chronic hypertension, urogenital infection and intrauterine growth retardation (IUGR). A pregnant woman was diagnosed as having preeclampsia when the arterial blood pressure was >140/90 mm Hg or when the blood pressure was at least 30 mm Hg above the usual systolic blood pressure and 20 mm Hg above the usual diastolic blood pressure, together with an urinary albumin loss of >300 mg/dl. Chronic hypertension was described when the patient had hypertension before pregnancy or developed hypertension before the 20th week of pregnancy [18]. The diagnosis of IUGR was made antenatally by clinical examination (small symphysis-fundal height measurement for gestational age) or by intermittent third-trimester ultrasound fetal biometry, i.e. reduced biparietal diameter, femur length, head circumference and mean abdominal diameter [19, 20], and confirmed after birth. For every baby meeting the inclusion criteria, clinical assessment was performed using the Sarnat grading system and the Thompson score within first 24 h to diagnose neonates with HIE. All inborn babies were assessed between 1 and 6 h of birth by neonatologists in the unit (the principal investigator and colleagues), and outborn babies were assessed between 1 and 6 h after admission. The Thompson score was performed on Days 1, 2 and 3.

Medcalc® (version 12.3.0.0, MedCalc Software bvba, Belgium) was used for statistics.

Results

During the 14-month study period, 50 full-term and near-term infants were diagnosed as having perinatal asphyxia and admitted in the neonatal intensive care unit of the University Hospital of Kinshasa. Thirty-nine were inborn and 11 were outborn. There were 902 term deliveries at the University Hospital of Kinshasa during the period, of which 46 were stillborn. The incidence of perinatal asphyxia in the hospital was 45 per 1000 live births.

The main maternal and neonatal characteristics are shown in Table 1. There was a high maternal age (31 years) and a high incidence of preeclampsia (20%), and 30% of the babies were delivered by cesarean section. HIE was present in 88% of the patients; Sarnat grade in the first 24 h was 1 in 16 patients, 2 in 20 patients and 3 in 8 patients. Thompson score in the first 24 h was >7 in 30 (60%) patients, of whom 6 had a Thompson score of >14. Fourteen (28%) of the 50 neonates died in the neonatal period.

Table 1

Maternal and neonatal characteristics

Maternal Number (n = 50) 
Median maternal age (years) (range) 31 (14–45) 
Primiparity (%) 16 (32%) 
Complications of pregnancy (%)  
    Preeclampsia 11 (20%) 
    Chronic hypertension 1 (2%) 
    Urogenital infection 6 (11%) 
    Intrauterine growth retardation (IUGR) 4 (8%) 
    Placenta previa 5 (9%) 
    Emergency cesarean delivery (%) 15 (30%) 

 
Neonatal Number (n = 50) 

 
Male gender (%) 25 (50%) 
Median post-menstrual age (weeks) (range) 38.8 (36.5–42) 
Median Apgar score (range)  
    At 1 min 4 (0–7) 
    At 5 min 5 (2–6) 
    At 10 min 6 (1–9) 
Mild encephalopathy (%) 16 (32%) 
Moderate encephalopathy (%) 20 (40%) 
Severe encephalopathy (%) 8 (16%) 
Maternal Number (n = 50) 
Median maternal age (years) (range) 31 (14–45) 
Primiparity (%) 16 (32%) 
Complications of pregnancy (%)  
    Preeclampsia 11 (20%) 
    Chronic hypertension 1 (2%) 
    Urogenital infection 6 (11%) 
    Intrauterine growth retardation (IUGR) 4 (8%) 
    Placenta previa 5 (9%) 
    Emergency cesarean delivery (%) 15 (30%) 

 
Neonatal Number (n = 50) 

 
Male gender (%) 25 (50%) 
Median post-menstrual age (weeks) (range) 38.8 (36.5–42) 
Median Apgar score (range)  
    At 1 min 4 (0–7) 
    At 5 min 5 (2–6) 
    At 10 min 6 (1–9) 
Mild encephalopathy (%) 16 (32%) 
Moderate encephalopathy (%) 20 (40%) 
Severe encephalopathy (%) 8 (16%) 

A good correlation (r = 0.77; p < 0.0001; 95% CI 0.5313–0.8470) was found between the Thompson score and the Sarnat grade at Day 1, as shown in Fig. 1. There was also a good correlation between the Thompson score and death and between the Sarnat grade and death, as shown in Figs 2 and 3.

Fig. 1.

Comparison between Thompson score and Sarnat grade at Day 1. The correlation between the Sarnat grade and the Thompson score was r = 0.77 (p < 0.0001; 95% CI: 0.5313–0.8470).

Fig. 1.

Comparison between Thompson score and Sarnat grade at Day 1. The correlation between the Sarnat grade and the Thompson score was r = 0.77 (p < 0.0001; 95% CI: 0.5313–0.8470).

Fig. 2.

Relation between Thompson score at Day 1 and death. There was a good correlation between the Thompson score at Day 1 and mortality (r = 0.42; p = 0.0024; 95% CI: 0.16–0.63).

Fig. 2.

Relation between Thompson score at Day 1 and death. There was a good correlation between the Thompson score at Day 1 and mortality (r = 0.42; p = 0.0024; 95% CI: 0.16–0.63).

Fig. 3.

Relation between Sarnat grade and death. There was a good correlation between the Sarnat grade at Day 1 and mortality (r = 0.42; p = 0.002; 95% CI: 0.17–0.63).

Fig. 3.

Relation between Sarnat grade and death. There was a good correlation between the Sarnat grade at Day 1 and mortality (r = 0.42; p = 0.002; 95% CI: 0.17–0.63).

Discussion

The study aimed to determine the incidence, etiologies and HIE score at the first day in newborns with perinatal asphyxia in the setting of a university hospital in DR Congo. The incidence of perinatal asphyxia in the University Hospital of Kinshasa remains at ∼40 per 1000 live births since 5 years. One could assume that this incidence is lower than in 1999, but we think this discrepancy is due to the fact that the study performed in 1999 took into account both term and preterm newborns. The incidence in this study is lower than the one reported by Cissé, Kinoti and Klingenberg, respectively, in Mali, East-Southern Africa and Tanzania [21]. But, it is higher than the incidence from Oswyn in New Guinea [22] and still remains 10 times higher than in the developed countries. We do not know the population-based incidence in low-income countries, as all the reported incidences are hospital-based.

Although 90% of the mothers attended prenatal consultations, preeclampsia and hypertension were the most important prenatal diagnosis (22%), followed by urogenital infections (11%) and IUGR (8%). This is comparable with studies by Kumar [7], Chen et al. [23] and Schneider [24]. We found four cases (8%) of IUGR, of which two were associated with preeclampsia and one with chronic hypertension. It is known that uteroplacental vascular insufficiency in humans is a common cause of IUGR and is associated with an increased incidence of perinatal asphyxia and neurodevelopmental disorders compared with normal-weight newborns. Experimental studies state that piglets and rats with IUGR showed a significantly greater amount of apoptosis in response to the hypoxia than the normal-weight piglets and rats, suggesting an increased vulnerability to apoptosis in these IUGR animals [25, 26]. We report six cases (11%) of urogenital infections, including urinary (cystitis and pyelonephritis) and genital (vaginitis, vulvitis, cervicitis and intrauterine infection) infections, defined clinically, biologically or bacteriologically. Intrauterine infection and inflammation are often associated with asphyxia. Proinflammatory cytokines are thought to be major mediators in brain injury in neonates with perinatal asphyxia, bacterial infection or both, and new insights into mechanisms underlying neural cell death in this condition might open new horizon for preventive and therapeutic strategies [27–29]. The median age of the mothers was 31 years. Ninety percent of the mothers followed attended prenatal consultations, and 78% of the deliveries were in the University Hospital of Kinshasa. Fifteen babies were born by cesarean section (30%), with acute fetal distress as the main indication in 60%. Only 32% of the babies were first-born. Although often factors like young mothers, lack of prenatal follow-up and home births are often mentioned as causes of perinatal asphyxia in low-income countries, this was not shown in this study. On the other hand, there was a high incidence of preeclampsia and hypertension. Infection did not seem to be a major contributor.

The incidence of HIE in patients with perinatal asphyxia was 88%, which was higher than reported by Penela-Velèz de Guevara et al. [30] in Spain (45% of HIE) and Oswyn et al. [22] in Papua New Guinea (27.2% HIE). Thirty patients (60%) had a Thompson score of >7 at Day 1; among them, six had a Thompson score of >14 at Day 1. The positive correlation between the Sarnat and the Thompson score confirms the validity of the clinical examination.

Although further study is needed to explain and prevent the high incidence of perinatal asphyxia in this group of patients, possible therapeutic strategies for the neonate with HIE need to be discussed. Cooling is now established as a standard therapy for HIE in term neonates in the developed world. It has a number needed to treat of 1 in 6–8, which is extremely successful [31–33]. In DR Congo alone, there were 2 824 389 births in 2010. With an incidence of perinatal asphyxia of at least 40 per 1000 live births, ∼113 000 babies would be born with perinatal asphyxia, of which 90 000 infants would have hypoxic ischemic encephalopathy. Extrapolating these figures of this study, ∼54 000 infants would be eligible for cooling; however, this will only be possible in the better-equipped hospitals in DR Congo. As children with a handicap have major problems for health care and survival, cooling might also be efficient economically. However, the cooling devices that are currently on the market are still expensive for these countries. A cooling device should be servo-controlled because the nursing supervision and monitors are less well-developed. A possible solution was recently published by Horn et al. [34]. A second important problem is the absence of ventilators. Most cooled patients are ventilated and receive morphine for pain therapy. This is an important problem in these countries. Babies with a Sarnat grade 3 at Day 1 and a Thompson score of 14 or more had a high mortality in our study, and this was also described by Robertson et al. [35]. In this way, not only entry criteria for cooling but also exclusion criteria might be necessary in these countries, and the question remains whether cooling should be started in this group of patients with high Thompson scores. Further studies using amplitude-integrated electroencephalography together with the Thompson score are currently performed in our unit to further define inclusion criteria.

We performed this study in preparing a safety study for early neuroprotective intervention. Therefore, we assessed HIE early after birth, i.e. within 6 h; however, some patients, mainly outborn, have been assessed later (between 6 and 24 h). Further, infants were not assessed until Day 7. This is a limitation to the study. A second limitation is that the study only described 50 patients in a University Hospital, which does not make it possible to extrapolate these results for the whole country of DR Congo. In the future, studies on perinatal asphyxia and HIE will have to assess HIE early (within 6 h of birth) as an entry criterion for neuroprotective intervention [31] and then evaluate infants until Day 7. In our setting, this might be possible if focusing on inborn infants only.

Conclusion

Perinatal asphyxia in Congo is like in low-incomes countries with regard to its etiologies and presentation, except the higher rate of HIE. Using a Thompson score of >7 as an entry criterion for cooling may be appropriate, with the limitation that the Thompson score was not obtained within 6 h in all the infants. In this study, 60% of the patients would be eligible. However, mainly because there is no possibility for ventilation, 11 of the 30 patients (37%) with a Thompson score of >7 died. Inclusion criteria for neuroprotective therapies in DR Congo will have to be adapted to the availability like ventilation and other intensive care treatments. Together with introduction of neuroprotective therapies, special attention should be given to further improvement of antenatal and perinatal care.

Funding

Therese Biselele is partly funded by UNIFOS (Universitair Fonds voor Ontwikkelingssamenwerking) KU Leuven.

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