Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya

Objective To describe the patient population, priority diseases and outcomes in newborns admitted <48 hours old to neonatal units in both Kenya and Nigeria. Study design In a network of seven secondary and tertiary level neonatal units in Nigeria and Kenya, we captured anonymised data on all admissions <48 hours of age over a 6-month period. Results 2280 newborns were admitted. Mean birthweight was 2.3 kg (SD 0.9); 57.0% (1214/2128) infants were low birthweight (LBW; <2.5kg) and 22.6% (480/2128) were very LBW (VLBW; <1.5 kg). Median gestation was 36 weeks (interquartile range 32, 39) and 21.6% (483/2236) infants were very preterm (gestation <32 weeks). The most common morbidities were jaundice (987/2262, 43.6%), suspected sepsis (955/2280, 41.9%), respiratory conditions (817/ 2280, 35.8%) and birth asphyxia (547/2280, 24.0%). 18.7% (423/2262) newborns died; mortality was very high amongst VLBW (222/472, 47%) and very preterm infants (197/483, 40.8%). Factors independently associated with mortality were gestation <28 weeks (adjusted odds ratio 11.58; 95% confidence interval 4.73–28.39), VLBW (6.92; 4.06–11.79), congenital anomaly (4.93; 2.42–10.05), abdominal condition (2.86; 1.40–5.83), birth asphyxia (2.44; 1.52–3.92), respiratory condition (1.46; 1.08–2.28) and maternal antibiotics within 24 hours before or after birth (1.91; 1.28–2.85). Mortality was reduced if mothers received a partial (0.51; 0.28–0.93) or full treatment course (0.44; 0.21–0.92) of dexamethasone before preterm delivery. Conclusion Greater efforts are needed to address the very high burden of illnesses and mortality in hospitalized newborns in sub-Saharan Africa. Interventions need to address priority issues during pregnancy and delivery as well as in the newborn. The study was approved by the Research and Ethics Committee at the Liverpool School of Tropical Medicine (protocol number:18–0210), The Lagos University Teaching Hospital Health Research Ethics Committee (protocol number: AMD/DCST/HREC/APP/2514), The Kenya Medical Research Institute-Scientific and Ethics Review Unit (protocol number: KEMRI/SERU/CGMR-C/120/3740) and the research and ethics committees at The Jaramogi Oginga Odinga Teaching and Referral Hospital (protocol number: ERC.IB/VOL.1/510), University College Hospital Ibadan (protocol number: UI/EC/18/0446), Massey Street Children’s Hospital (protocol number: LSHSC/2222/VOL.VIB/185), Ahmadu Bello University Teaching Hospital (ABUTH/HZ/HREC/D37/2018), and Maitama District Hospital (protocol number: FHREC/2018/01/108/19-09-18). The study was conducted in five NNUs in Nigeria of which four provide tertiary level care (University College Hospital, Ibadan; Lagos University Teaching Hospital, Massey Children’s Hospital, Lagos; Ahmadu Bello University Teaching Hospital, Zaria) and one secondary level neonatal care (Maitama District Hospital, Abuja) and two in Kenya: Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu providing tertiary level and Kilifi County Referral Hospital secondary level neonatal care. In Nigeria, the Nigeria Society of Neonatal Medicine led in the selection of these facilities and aimed to incorporate neonatal units from both the northern and southern parts of the country. In Kenya, the facilities were chosen based on previous collaborative partnerships aiming to include neonatal units that provide different levels of care i.e. tertiary and district level in different regions of the country. The basis of this selection process was prior research and clinical training collaborative partnerships between the Liverpool School of Tropical Medicine (LSTM) co-investigators and clinical researchers in Nigeria and Kenya. All neonatal units admitted both inborn and outborn infants <28 days of age. All neonatal units except one in Kenya had separate rooms/wards for admitting inborn and outborn neonates. The tertiary level units typically had 2–4 consultant neonatologists or paediatricians who supervised resident doctors/registrars, intern house officers, clinical officers and a team of 1–3 nurses per shift. In all the units, the neonates were admitted by intern house officers, medical officers or clinical officers and were reviewed by a consultant neontologist or paediatrician daily during their admission. The bed capacity ranged from 24–80 but occupancy often exceeded 100%. The district level NNUs had 1–3 consultant paediatricians who worked with medical officers, clinical officers and a team of 2–3 nurses per shift. The bed capacity ranged from 12–27. The NNUs provide care according to institutional neonatal protocols in Nigeria and the Kenya national paediatric protocol [20]. All the NNUs had access to oxygen, pulse oximetry and phototherapy but these were often limited in availability and, therefore, reserved for the sickest newborns. All the tertiary level NNUs and one of the district level NNUs used non-invasive ventilation (i.e. continuous positive airway pressure), but none used endotracheal ventilation. This was a multi-centre, prospective, observational study. During network meetings held before data collection, we established a standardised case report form (CRF) and an anonymised demographic/clinical database. Clinical criteria, laboratory analyses and imaging currently used for the diagnosis of common neonatal morbidities were reviewed and additional CRFs developed to capture episodes of suspected sepsis, respiratory problems, abdominal conditions and birth asphyxia diagnosed according to current clinical practice in each NNU. The CRFs are available from https://www.lstmed.ac.uk/nnu. All newborns aged <48 hours admitted to each NNU over a 6-month period between August 2018 and May 2019 were included in the study and had CRFs completed with the period of data collection determined by timing of ethics approval. Infants who were ≥ 48 hours of age at admission were excluded because we wanted to optimize recall of information on feeding practices from birth. In addition, infants aged 48 hours and above were generally admitted to paediatric wards rather than neonatal units. Details of maternal demography, socioeconomic status, health and the current pregnancy were recorded from ante-natal records. Details of labour and delivery were collected from hospital records. Paper CRFs were kept as part of infant case records or stored separately and updated during NNU admission. Details of clinical criteria used to diagnose infant conditions were recorded in separate forms, the analyses of which are provided in a separate manuscript that is in preparation. Data clerks in each NNU entered data into a REDcap database (http://www.project-redcap.org/), that was hosted by the Liverpool School of Tropical Medicine (LSTM). Infants were identified by a unique study number only and no personal identifiers were recorded in the database. Categorical variables were presented as frequencies and percentages. Normally distributed variables were reported using means and standard deviations (SDs) and median and interquartile ranges (IQRs) were used for non-normally distributed variables. We analysed variables according to country and level of care to provide some insights into the variability between NNUs. When evaluating differences between individual NNUs, country and level of care, we considered the clinical relevance of differences in variables as well as statistical significance. Except for five variables with ≥10% missing data (maternal HIV status, hepatitis B, syphilis, gestational diabetes, and infant length of admission), the average percentage of missing data for variables ranged from 0–6.3%. The five variables with a high percentage of missing data were not included in the multivariable logistic regression analysis. Univariate and multivariable logistic regression analyses identified factors associated with mortality with data imported into Stata version 15.0 (Stata Corp). Multivariable logistic regression odds ratio plot was performed by R V3.5.2. Kaplan-Meier survival analysis was used to estimate the independent effects of gestation and birthweight on neonatal mortality. Mothers/infants with missing data for a variable were not included in the analyses. Information about the collection of anonymised data was displayed in each NNU; no parents chose to opt-out of the study. At one of the Network sites, parents provided written informed consent; 82 parents declined consent at this site. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.