The study finds that early systematic pediatric care may significantly reduce the neonatal morbidity of infants with associated CL/P in South America who survive the neonatal period, for whom the intervention reduced hospitalization stay by about six days. This suggests that systematic pediatric care may significantly reduce inpatient costs of associated cases. In the US, first year of life healthcare costs for infants with associated CL/P exceed those of unaffected children by more than 25 times [16
]. As studies evaluate the effectiveness of primary prevention programs for CL/P such as folic acid supplementation [33
], tertiary prevention programs are essential for reducing the health risks and economic burden of CL/P for affected individuals and families. About half of the neonatal hospital readmissions in the treatment group were due to respiratory, weight loss, or feeding and nutrition problems. This highlights the adverse oral-cleft effects on early health and the importance of providing adequate advice and training to parents before hospital discharge after birth about optimal household approaches to reduce these health problems, especially the feeding problems.
There was a markedly larger benefit from the intervention for reducing hospitalizations in the associated than the isolated group. This is likely due to the greater health needs and more frequent and longer hospitalizations among the associated group that may be responsive to the intervention. On average, infants in the associated control group were hospitalized for about 10 days between the 7th and 28th days of life, compared to about 2 days for the isolated control group. This highlights the significantly elevated health problems among the associated group. This differential effect between the isolated and the associated group is consistent with the theory that the intervention is more relevant on average for infants with greater health needs that can be identified and addressed by the intervention.
Congenital anomalies are a leading cause of neonatal mortality and morbidity worldwide [34
]. Despite substantial progress in achieving the Millennium Development Goals in reducing under-five mortality worldwide, there has been far less improvement in neonatal mortality [34
]. The study suggests that increasing access to systematic pediatric care alone may not reduce the contribution of congenital anomalies to neonatal mortality. A potential contributor to this result is that CL/P impose a larger burden on infant survival immediately after birth and during the first few days of life during which infants typically are hospitalized. After that, mortality risks drop significantly in both the isolated and associated groups. About 62% and 76% of deaths in the isolated group occurred by the 7th
day of life, respectively. Similarly, 75% of deaths in the associated group occurred by the 7th
day of life. The study's intervention began on the 7th
day of life given that at-risk infants generally remain hospitalized during the first few days of life and receive standard in-patient pediatric care. Further, CL/P in the associated groups are associated with major structural limitations and malformations including cardiac and neural tube abnormalities that may reduce the intervention effects on survival.
The study is among the first studies to estimate mortality rates among infants with CL/P in South America. The results provide evidence that neonatal mortality and morbidity are very high among infants with associated CL/P in South America and that CL/P mortality rates are higher in South American countries than the US [11
]. Hujoel et al (1992) report that neonatal mortality rates of infants with CL/P in the state of Washington in 1984-1988 were about 1.6% in the isolated group and 31.2% in the associated group [13
]. Druschel et al. (1996) report that first-year mortality rates of infants with CL/P in New York State between 1983 and 1991 were about 1% in the isolated group and 23.5% in the associated group [11
The study finds significant ethnic disparities in neonatal mortality of infants with CL/P in South America, with significantly higher risks among infants with African and Native ethnic ancestry compared to other ancestries. Racial disparities in infant health outcomes have been documented in several of the study countries [36
], consistent with the study findings. For example, neonatal and infant mortality rates in Brazil are twice as high among children of black or mixed race women as whites [37
]. Identifying and targeting the contributing factors is needed for reducing disparities. Cleft lip with/without palate, lower birth weight, shorter gestational age and the presence of multiple malformations besides CL/P are additional risk factors for neonatal mortality risk that can be routinely evaluated to identify infants with CL/P who are at higher mortality risks. The greater mortality risk among cases with cleft lip compared to cleft palate alone is surprising, especially in the case of cleft lip alone. It is unclear what factors are driving this result. It is possible that cleft lip may be associated with greater parental stress and anxiety in the neonatal period compared to cleft palate alone, which may have adverse effects on the infant's household environment and care. More research is needed to identify the reasons for this increase in mortality risks.
One study limitation is the use of a non-randomized control group. As mentioned above, the investigators considered randomization to be unethical. However, the similarity between the study intervention and control groups on most baseline characteristics supports the utility of identifying a natural control group born in a very close period to the intervention group in the same communities when randomization is infeasible. Furthermore, adjusting for the relevant baseline characteristics is expected to account for any differences between the two groups that may bias the treatment effect estimates.
The study provides an intervention model and research design that may be implemented in other studies to evaluate the effects of early systematic pediatric care on the neonatal survival and health of infants born with other common and burdensome birth defects. Such birth defects include neural tube defects, congenital heart anomalies and Down Syndrome which also have high mortality and morbidity especially in less developed countries [38