Prospective study of early and late outcomes of extremely low birthweight in Central Saudi Arabia

Over the past five decades, mortality of preterm neonates has steadily decreased [1–4]. The 50% limits of viability of infants has decreased to 23 to 24 weeks during this decade as compared to 30 to 31 weeks in the 1960s [4] This improvement in survival might be due to the changes in the methodologies of neonatal intensive care, new modes of respiratory support for neonates with respiratory distress, and development of a safety culture with the training of clinicians to work together in this culture [5].

Very preterm neonates showed significant improvement in the neurodevelopmental outcome over this period, yet this improvement lagged behind that of survival [1, 2, 4–6]. Cognitive and neurologic impairments were common among extremely preterm children at school age, as compared with their classroom peers [7, 8]. Long-term health and educational needs were required at the age of 8 years, for ELBW who were born in the 1990s [9]. Those ELBW infants, when examined for cognitive and behavioral outcomes at school age, showed an IQ that was nearly two-thirds SD below that of healthy controls [10].

Very preterm infants are influenced by multiple factors that affect their survival and long-term neurodevelopmental outcome. Those who are born at large perinatal–neonatal centers, have survival advantage, because of the availability of health care providers who have vast experience in providing perinatal and neonatal care as well as comprehensive multidisciplinary operational structure [4, 11].

The lower limit of viability was set as 22 weeks of gestational age (GA) or 500 g birth weight, by the WHO [12], 22 completed weeks (154 days) gestation and ending 7 complete days after birth, by the International Classification of Diseases [13], 22 completed weeks of gestation, (instead of 24 weeks), by the Eugenic Protection Act in Japan [14] and 23 weeks GA and/or 400 g in birthweight, by the American Academy of Pediatrics [15]. These amendments may encourage physicians to fully resuscitate these infants at the delivery room without considering the high mortality and morbidity [16].

In Saudi Arabia, there are no written guidelines on the definition of the lower limit of viability, and there has been a call for such limit [16]. Obstetric measures for the prevention of preterm delivery need to be optimized in order to decrease the morbidity and mortality associated with extremely low birthweight infants. To achieve this goal, the outcome of extremely low birth weight Saudi infants should be understood. This study aimed to determine the survival rate of extremely low birthweight infants delivered at King Abdulaziz Medical City (KAMC), at different values of birth weight and gestational age, to determine the lower limit of viability and survival outcome, and to determine the incidence of neurodevelopmental impairments and cognitive abnormalities 3 to 6 years after birth.

Mortality rate was significantly higher among female infants (p = 0.021), those with lowest gestational age (p = 0.002), those with lowest birth weight (p < 0.001) and those delivered vaginally (p = 0.025). With regard to timing of death, one-third died within 3 days after delivery (35.4%) and one-third after 28 days (31.3%). Table 1.

Birthweight-specific mortality for all ELBW infants is shown in Fig. 2. Mortality rate decreased steadily with increasing birthweight between 450 and 995 g, ranging from 84% for 450–600 g infants to 22% for 801–995 g infants. The 50% limits of viability was that with a birthweight of > 600 g.

The gestational age-specific mortality for all ELBW infants is shown in Fig. 3. Mortality decreased steadily through a gestational age of 28 weeks, ranging from 100% at 22 weeks. to 23% at 26–28 weeks., and then rose slightly for infants between 29 and 30 weeks. The 50% limit of viability was that at week 25 of gestation.

Survival of ELBW neonates has improved with the widespread use of exogenous surfactant agents, maternal steroids, and advancements in neonatal technologies. In our study the overall survival rate was 59%. Mortality rate was associated with both birthweight and gestational age. Mortality rate decreased steadily with increasing birth weight between 450 and 995 g, ranging from 84% for 450–600 g infants to 22% for 801–995 g infants. It decreased steadily through a gestational age of 28 weeks, ranging from 100% at 22 wks. to 23% at 26–28 weeks, and then rose slightly for infants between 29 and 30 weeks, possibly due to the greater incidence of growth retardation and congenital malformations at later gestational ages. The Royal Women’s Hospital in Australia reported death rates of 54% at 23 weeks and 32% at 24 weeks [20]. The corresponding death rate figures in our study were 84% and 48% respectively.

In Japan, where neonatal medical care was the highest quality care in the world, as reported by the WHO in 2005, the viability of ELBW infants with a 50% survival rate, were those at week 23 of gestation or with a birthweight of 500 g [21]. However, in our study, the 50% limits of viability were 25 weeks’ gestation and > 600 g birthweight. It has been summarized in the literature that infants born at < 23 weeks’ gestation and < 500 g are too immature to survive, and provision of care for these infants is unreasonable, while infants who are born at ≥25 weeks’ gestation and with a birth weight of ≥600 g are mature enough and warrant initiation of intensive care [4].

Fetal mortality rates in European countries were higher when based on a 28-week gestational age threshold compared with a 1000 g birthweight threshold [22]. In Japan, the predictors of survival of ELBW infants were GA at delivery, Apgar score at 5 min, antenatal steroid and birthweight [21]. However, in our study, these predictors were birthweight and Apgar score. Fetal growth restriction is a reflection of underlying pregnancy complications [22], and a risk factor of more than 80% of fetal deaths in high-income countries, [23] and may contribute also to lower birthweights [24].

In spite of the reduction in mortality with the use of surfactants, no significant improvement in morbidities such as; chronic lung disease, cerebral palsy, neurosensory deficits and cognitive delays, was reported among surviving infants [9, 25, 26]. In our study, pediatric assessment by DDST revealed high incidence of developmental delays, cerebral palsy, delayed speech and stuttering and wasting. The study by Marlow et al. [7] on 6-year old children born at less than 26 weeks’ gestation in England revealed common cognitive and neurologic impairment with rates ranging from 22 to 34%. The incidence of cerebral palsy among ELBW children in our study is extremely high (36.2%) when compared with figures of 16 to 21% in previous studies [7, 27, 28]. However, direct comparison between our figures and figures of previous studies may be difficult because of the lack of consistency in the outcome measures, and information on the policy of intensive neonatal care and outcome measures in these institutions from which these figures were derived [7, 29, 30].

Psychological assessment using Wechsler test for IQ at the age of 6 years revealed that 10% of children were intellectually disabled [6.7% mild & 3.3% moderate], in addition to 11.7% borderline or slow learners. In Anderson’s study, [30] the mean IQs for ELBW children were in the average range (range, 90–109; mean, 95.5), and they were below the IQs of normal birth weight children. In our study, the mean IQ for ELBW children was below the average range (range, 49–128; mean, 86.75). These findings indicate that adverse cognitive sequelae are a more frequent outcome among such infants, and this would explain the future educational difficulties that have been reported for ELBW children [31].

In conclusion, more than one-third of ELBW died before discharge from NICU, and two-thirds of survivors had one or more neurodevelopmental and/or cognitive abnormalities during their first 6 years of life. The study showed that 50% limits of viability of ELBW infants were those at week 25 of gestation or with a birthweight of more than 600 g. These limits are higher than those reported in other studies. However, birth weight, in our study, was the only significant predictor of survival of ELBW infants. These findings might reflect the fact that improving survival rates for the tiniest babies would result in large numbers of disabled children in the community.

Consequently, routine aggressive resuscitation of newborns at 23 weeks and/or with < 600 g. birth weight should be approached with caution. Given the complexity of the issues, the approach to resuscitation of infants at 23 weeks must account for the perspectives of the birth mother and her family, obstetricians, and pediatricians. Thus, the process of care of ELBW needs to be revisited so as to take into consideration the findings of the present study. A multicenter study is recommended to include different types of hospitals in the kingdom and in the region, as the outcome of these infants varies from hospital to another, based on the facilities available and on the attitude of the staff of neonatal intensive care units, whether they are proactive or selective in management of those ELBW infants.