Original Article

Seasonal Variation in Solar Ultra Violet Radiation and Early Mortality in Extremely Preterm Infants Ariel A. Salas, MD, MSPH1 Kelly A. Smith, MSPH2 Namasivayam Ambalavanan, MD2 1 Department of Pediatrics, The Children’s Hospital of Philadelphia,

Philadelphia, Pennsylvania 2 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama

Mackenzie D. Rodgers, MD2

Vivien Phillips, RN2

Address for correspondence Ariel A. Salas, MD, Department of Pediatrics, The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, Suite 9NW65, Philadelphia, PA, 19104 (e-mail: [email protected]).

Abstract

Keywords

► ► ► ► ► ►

ultraviolet radiation ultraviolet rays sunlight exposure vitamin D synthesis epidemiology premature infants

Background Vitamin D production during pregnancy promotes fetal lung development, a major determinant of infant survival after preterm birth. Because vitamin D synthesis in humans is regulated by solar ultraviolet B (UVB) radiation, we hypothesized that seasonal variation in solar UVB doses during fetal development would be associated with variation in neonatal mortality rates. Methods This cohort study included infants born alive with gestational age (GA) between 23 and 28 weeks gestation admitted to a neonatal unit between 1996 and 2010. Three infant cohort groups were defined according to increasing intensities of solar UVB doses at 17 and 22 weeks gestation. The primary outcome was death during the first 28 days after birth. Results Outcome data of 2,319 infants were analyzed. Mean birth weight was 830  230 g and median gestational age was 26 weeks. Mortality rates were significantly different across groups (p ¼ 0.04). High-intensity solar UVB doses were associated with lower mortality when compared with normal intensity solar UVB doses (hazard ratio: 0.70; 95% confidence interval: 0.54–0.91; p ¼ 0.01). Conclusion High-intensity solar UVB doses during fetal development seem to be associated with risk reduction of early mortality in preterm infants. Prospective studies are needed to validate these preliminary findings.

Measuring the interaction between environment and health outcomes is difficult. Nevertheless, many ecologic studies have reported lower mortality rates in several geographically and ill-defined populations exposed to increasing intensities of solar ultraviolet B (UVB) radiation most likely as a result of increased vitamin D synthesis.1,2 Vitamin D production during pregnancy seems to be critical to promote normal fetal lung development3–6 and consequently decrease the risk of severe respiratory distress syndrome (RDS) after preterm birth, a major determinant of infant mortality.7 The large variation in mortality and respiratory morbidity among infants born before 28 weeks

gestation across U. S. hospitals, despite adjustment for common clinical variables suggests the presence of unmeasured factors that affect the course of lung disease in extremely preterm infants.8 Seasonal variation in solar UVB radiation and consequent variation in vitamin D production during fetal lung development could be one of those unmeasured factors contributing to variation in mortality rates of extremely preterm infants at high risk for RDS and surfactant deficiency. We hypothesized that seasonal variation in UVB doses at 17 and 22 weeks gestation would be associated with variation in risk of early mortality in preterm infants.

received February 15, 2015 accepted after revision April 15, 2015

Copyright © by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.

DOI http://dx.doi.org/ 10.1055/s-0035-1554797. ISSN 0735-1631.

Downloaded by: University of Florida. Copyrighted material.

Am J Perinatol

Salas et al. There were nearly equal proportions of black (55%) and white (40%) infants in the three cohort groups (►Table 1). Mortality rates within the first 28 days after birth were significantly different according to increasing intensity of local solar UVB doses at 17 and 22 weeks gestation (p ¼ 0.04) (►Fig. 1). After adjustment for covariates, the relative likelihood of early mortality was lower for infants in the high intensity local solar UVB dose group compared with infants in the normal intensity local solar UVB dose group (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.54–0.91; p < 0.01). Low intensity local solar UVB doses were not associated with increased neonatal mortality when compared with normal intensity local solar UVB doses (HR: 1.12; 95% CI: 0.84–1.46; p ¼ 0.44). Each additional year in maternal age was not associated with increased mortality in the adjusted model (HR: 0.76; 95% CI: 0.43–1.31; p ¼ 0.32). Each 100 g increment in BW (HR: 0.32; 95% CI: 0.20–0.50; p < 0.01) and each additional week in GA (HR: 0.11; 95% CI: 0.07–0.18; p < 0.01) were associated with reduced mortality. Nonblack race was associated with increased mortality risk (HR: 1.43; 95% CI: 1.18– 1.74; p < 0.01). Similarly, male sex (HR: 1.25; 95% CI: 1.02– 1.74; p ¼ 0.03) was associated with an increased risk of mortality (►Table 2). The association between high intensity local solar UVB doses and risk reduction of early mortality was stronger and statistically significant in infants born to nonblack mothers (HR: 0.61; 95% CI: 0.37–0.99; p ¼ 0.04) compared with infants born to black mothers (HR: 0.75; 95% CI: 0.52–1.06; p ¼ 0.11).

Methods For this retrospective cohort study, infants born alive with gestational age (GA) between 23 and 28 weeks gestation admitted to the Neonatal Intensive Care Unit of the University of Alabama at Birmingham between July 1996 and December 2010 were included. Infants with major congenital anomalies were excluded. The study was approved by the University of Alabama at Birmingham Institutional Review Board. Three infant cohort groups were defined according to increasing intensities of local solar UVB doses at early stages of fetal lung development (17 and 22 weeks gestation).2 Based on the standardized UV Index Scale,9 a 7-day average UV Index at 17 and 22 weeks gestation was calculated for all infants included in the study. Intensity of the local solar UVB dose was categorized as follows: low if both 7-day average UV indexes at 17 and 22 weeks gestation were between 0 and 2 (low-intensity local solar UVB dose group), normal if both 7day average UV indexes were between 3 and 5 (normal intensity local solar UVB dose group), and high if both 7day average UV indexes were between 6 and 15 (highintensity local solar UVB dose group). Dates for 17 and 22 weeks gestation were estimated based on date of birth and GA at birth. Solar UVB radiation data at latitude 33 degrees North were extracted from the National UV index report available at: http://www.cpc.ncep.noaa.gov/products/ stratosphere/uv_index/uv_annual.shtml. Death within the first 28 days after preterm birth was the primary outcome of the study. Time-to-event analysis and proportional hazard regression were used to determine whether the estimated probability of survival was significantly different across the three infant cohort groups. GA, birth weight (BW), race, sex, birth year, and maternal age were included as covariates in the adjusted model. All data were analyzed using SAS 9.3 (SAS Institute. Inc., Cary, NC).

Discussion Our findings suggest that seasonal variation in solar UVB radiation at early stages of fetal lung development is associated with variation in mortality rates of extremely preterm infants. The difference in mortality rates according to increasing intensity of solar UVB doses was statistically significant and independent of race, BW, and GA; however, a linear dose– response relationship was not found. Only high intensity local solar UVB doses were associated with a significant risk reduction of early mortality in preterm infants. The most likely physiological mechanism responsible for the observed association is vitamin D synthesis.10,11

Results Outcome data at 28 days after birth was available in 2,319 infants. The overall mortality rate at 28 days after birth was 18%. The mean BW of study participants was 830  230 g and the median GA was 26 weeks (interquartile range: 25–27).

Table 1 Baseline characteristics of extremely preterm infants according to increasing intensities of local solar UVB doses at 17 and 22 weeks gestation Low-intensity UVB dose group (n ¼ 527)

Normal intensity UVB dose group (n ¼ 1,091)

High intensity UVB dose group (n ¼ 701)

p-Value

950  290

820  220

830  220

< 0.01

GA in wks (mean  SD)

26.5  2.1

25.8  1.6

25.9  1.6

< 0.01

Female (%)

46

50

48

0.40

Black race (%)

55

54

58

0.32

Maternal age (mean  SD)

25.5  7.8

25.2  6.2

25.2  6.2

0.66

BW in g (mean  SD)

Abbreviation: UVB, ultraviolet B. American Journal of Perinatology

Downloaded by: University of Florida. Copyrighted material.

Variation in Solar UV Radiation and Neonatal Mortality

Fig. 1 Survival curves for three cohort groups of extremely preterm infants according to increasing intensities of local solar ultraviolet B doses at 17 and 22 weeks gestation.

Endogenous vitamin D production follows well-characterized patterns of seasonal variation in solar UVB radiation and ranges from 60 IU/d in winter to 1,200 IU/d in summer10 depending on latitude.2,8–12 At latitudes between 40 degrees South and 40 degrees North, vitamin D production during winter is constant and effective.9 At latitudes > 40 degrees North, vitamin D production during winter is minimal12 and results in greater seasonal variability of vitamin D deficiency. Latitude in Birmingham, Alabama (33 degrees North) could explain the lack of differences in mortality rates observed between low and normal intensity local solar UVB dose groups and the lower mortality rates found in the high intensity local solar UVB dose group. At latitudes between 40 degrees South and 40 degrees North, effective vitamin D production observed during summer might compensate lim-

Salas et al.

ited vitamin D production observed in late winter10,13 and reduce the variability in the prevalence of vitamin D deficiency throughout gestation and fetal development.14 The existing 6-week time interval between peak UVB doses and peak vitamin D concentrations in pregnant women11 suggests that high intensity local solar UVB doses at 17 weeks gestation could result in high maternal/fetal serum vitamin D concentrations around the time of delivery in preterm infants born before 28 weeks gestation. After 28 weeks gestation, vitamin D concentrations are strongly correlated with GA and higher values are associated with lower risk of preterm birth.15 Higher vitamin D concentrations during pregnancy are also associated with lower rates of low BW (

Seasonal Variation in Solar Ultra Violet Radiation and Early Mortality in Extremely Preterm Infants.

Vitamin D production during pregnancy promotes fetal lung development, a major determinant of infant survival after preterm birth. Because vitamin D s...
107KB Sizes 0 Downloads 5 Views