Gestational age and 1-year hospital admission or mortality: a nation-wide population-based study

The increased vulnerability of moderate preterm infants (moderate PT) (32^0/7-33^6/7 weeks of gestation) and late preterm infants (late PT) (34^0/7–36^6/7) in the neonatal period is now widely accepted [1‐5], and undoubtedly these infants have both excess morbidity and mortality [1‐9]. Recently, it has been shown that this is also relevant for early term infants (early PT) (37^0/7–38^6/7) compared with infants born full term (39^0/7–40^6/7) and post-date (≥41^0/7) [1, 2, 4, 6‐10].

Moreover, studies have identified an increased risk of hospitalization for late PT compared with full term infants within the year after discharge [11‐15]. A large epidemiological study conducted in California showed that the likelihood of any hospitalization in the first year of life decreased with advancing gestational age (GA), even inside the subgroup of infants categorized as late PT [11].

Therefore, the hypothesis of a continuous change in babies’ outcome according to completed weeks of gestation should be evaluated before revisiting the usual categorization of GAs. More information is also needed to: i) identify the respective contribution of each week of gestation in the prognosis of infants born after 31 weeks of gestation; ii) understand the associated morbidities, in order to reduce the hospitalization rate of these babies, as they account for a large proportion of births [11].

The objective of this nation-wide population-based study was to evaluate, in infants born after 31 weeks of gestation, the hospitalization rate and in-hospital mortality rate in the first year after birth, according to GA at birth.

In France, 9.8% of live-born neonates with GA ≥ 32 weeks were admitted to hospital between d1 and d28. An inverse relationship between GA and hospital admission or admission in NICU remained up to 40 weeks. The results of this study, which are in keeping with other French and international publications [1‐7, 12, 15, 22‐25], also confirmed that there was an inverse relationship between GA and in-hospital death from 32 – 40 weeks of gestation. Interestingly, a recent English study suggested that poor outcomes among late and early PT were not only due to physiological immaturity but also to the biological determinants of preterm birth whether they are spontaneous or medically indicated [7].

Overall results of our study fit well with the recent ACOG committee statement which highlighted that implementation of a policy to decrease the rate of non-medically-indicated delivery before 39 weeks has been found to improve the neonatal outcome [10].

More specifically, the usual categorization of deliveries by GA partially erases the continuum of prognosis with GA, especially in the category of “term” infants (37–40 weeks) and it is not sufficient for individual clinical decisions and accurate public health information in moderate and early PT.

Post-date infants were more likely to require neonatal and post-neonatal hospitalization compared to infants born at 40 weeks and the 43 weeks group was also at increased risk of neonatal mortality while the 42 weeks group was not. Even if any conclusion about the 43 weeks group must take into consideration the very small sample size, this result suggests that continued efforts to prevent post-date births and their complications are needed [26].

The mean duration of stay in the different neonatal care units fell with increasing GA. However, given the large number of early PT concerned, the care provided to them in neonatal care units accounted for 51.5% of the 490 986 hospitalization days required by babies born after 31 weeks of gestation. This information is important for the optimal organization of perinatal health. Similarly, even though the rate of hospitalization among late PT is low, this population is large and any increase in the size of this population may significantly affect the need for hospital beds [27].

Moreover, the detrimental effect of birth before 38 weeks was not limited to the neonatal period since both the hospital admission rate and the in-hospital mortality rate were increased in the post-neonatal period (d28–d365) in our study. A recent study of birth certificates in California showed that the odds ratios (ORs) for any hospitalization within 365 days of life steadily declined with GA with the exception of 35 to 37 weeks of gestation for which ORs plateaued or even rose with increasing GA [11]. Another study [24] of infants born at ≥ 33 weeks of gestation similarly reported the greater risk of hospitalization among infants born at 36 weeks. In contrast, this French study showed a constant declining rate of hospitalization with GA in the first year of life including hospitalization during the neonatal period. As the rate of any hospitalization in the first year of life was greater in France than in California [11] it could be suggested that reducing hospital admissions and shortening the length of hospital stays in late PT may favor rehospitalization. This hypothesis deserves further studies.

Our study showed an excess mortality in the first year after delivery at 37–38 weeks. A Swedish cohort study [28], similarly showed excess mortality not only in the post-neonatal period but also in infants aged from 1 – 5 years and in young adults for births at 37–38 weeks. Even though the cause of post-neonatal deaths could not be ascertained in our study, it is worth noting that the main causes of post-neonatal hospitalization were infections (bronchiolitis, gastroenteritis, ear, nose and throat diseases) and that the risk of post-neonatal hospitalization was closely related to low GA. Overall, these results suggest that the reinforcement of preventive measures against infant infections should be applied not only in preterm infants but also in early PT.

The in-hospital mortality rate in our study (0.85/1000 live births) was only one fourth of the infantile mortality rate reported in Metropolitan France (3.28 per 1000 live births in 2011) by the French Vital Statistics obtained from death certificates [29]. The difference was greater in the first 28 days (0.48 vs 2.21/1000) than in the d29-d365 period (0.48 vs 1.07/1000). The main causes of death in the first year of life in France were perinatal diseases (48.7%) and congenital malformations or chromosomal anomalies (21.1%) in the period 2000–2008 [29]. Therefore, most of the discrepancies between the in-hospital death rate and the French infantile mortality rate were probably due to births not included in this study (congenital malformations/chromosomal abnormalities and preterm births before 32 weeks), which have a high mortality rate [30] as also to the exclusion of multiple births. Other causes of death outside the hospital area are sudden infant death syndrome (8.82% of infantile mortality in France), accidents or death from other causes [31, 32].

Our results showed that the risk of post-neonatal hospitalization gradually increased from 32 to 40 weeks of gestation, even after adjustment for sex, pregnancy-related disease and initial hospitalization. However, other characteristics associated with the risk of post-neonatal hospitalization could not be ascertained in our population and this represents a limitation of our study. In a selected population of late PT, Shapiro-Mendoza and colleagues [33] found that risk factors for subsequent readmission were NICU stay less than 4 days, breastfeeding, Asian/Pacific Islanders, firstborn infants, and public payers at the time of delivery.

Therefore, special studies are now needed to obtain more knowledge on the health status of preterm infants hospitalized in the first month of life in order to identify the most high risk infants for morbidity and readmission.

Another limitation of this study is the lack of data about insufficient prenatal care and deprivation, which were found to be independent variables associated with infant hospital attendance or in-hospital death during the first year of life in several studies [31, 32].

This national study focused on more mature preterm infants and identified 40 weeks as the GA with the best prognosis in the first year of life. However, the universal value of 40 week as the optimal length of gestation cannot be inferred from this study as physiological factors may influence the physiological duration of gestation (multiplicity but also race, ethnicity) as well as medical practices. We therefore feel that other studies should be conducted in territories with different population characteristics and/or medical practices and/or perinatal health care systems.

The rates of hospital admission and in-hospital death were inversely related to GA below 39 weeks. This study confirmed that being born late preterm was a risk factor of increased morbidity and mortality but also extended this observation to infants born at early term. These findings should contribute to the redefinition of what constitutes term birth and to eventual modifications of medical practices. Non-medically indicated birth at 37 or 38 weeks should be discouraged [10] and conversely, the reason for medically indicated birth should be clearly indicated in medical files.