to determine whether race / ethnicity and sex independently increase risk of respiratory distress syndrome ( rds ) in late preterm and term infants . using a cohort design , we studied the risk of rds associated with race / ethnicity and sex in infants with gestational age ( ga ) 34 to 42 weeks born between 1 january 2000 and 31 december 2009 ( n=286  454 ) within 12 hospitals in the northern california kaiser permanente medical care program . male sex ( adjusted odds ratio ( aor ) 1.68 ; 95% confidence interval 1.45 to 1.93 ) and white race / ethnicity ( vs asians ( aor 0.57 ; 95% confidence interval 0.47 to 0.70 ) , blacks ( aor 0.66 ; 95% confidence interval 0.50 to 0.87 ) , and hispanics ( aor 0.76 ; 95% confidence interval 0.64 to 0.90 ) ) independently increase risk for rds regardless of ga . a ga < 39 weeks , operative delivery , maternal diabetes , and chorioamnionitis also increased rds risk in this cohort . male sex and white race / ethnicity independently increase risk for rds in late preterm and term infants . risk of neonatal respiratory distress syndrome ( rds ) is inversely associated with gestational age ( ga ) owing to developmental delay in production of the pulmonary surfactant . in extremely premature ( birth weight < 1000  g , < 27 weeks ga ) and very premature ( birth weight < 1500  g , < 32 weeks ga ) infants , male sex , maternal diabetes , white race , chorioamnionitis and operative delivery also increase risk and severity of rds . however , the associations of sex and race / ethnicity with rds risk have not been characterized in late preterm and term infants . when compared with term infants , late preterm infants ( 34 weeks and 36 weeks ga ) have higher rates of rds and other non - respiratory morbidities that often require technological and pharmacological interventions and prolonged hospital stays . although preterm and late preterm birth rates have declined in the last 5 years , a substantial fraction of infants ( 12.3% in the united states ) is still delivered before 37 weeks gestation , most of whom ( 70% ) are late preterm infants . term infants have increased risk of rds through 39 weeks of gestation . to determine whether race / ethnicity and sex independently increase risk of rds in late preterm and term infants , we used a standardized diagnosis of rds in a multihospital - based cohort of racially and ethnically diverse , late preterm and term infants from the northern california kaiser permanente medical care program ( nc - kpmcp ) . we found that male sex and white race / ethnicity independently increase risk for rds in late preterm and term infants . using a clinical information system employed at all nc - kpmcp facilities that links maternal and neonatal records and clinical records to multiple information systems ( for example , laboratory and hospitalization data ) , we identified all live - born infants delivered at 12 nc - kpmcp facilities between 1 january 2000 , and 31 december 2009 with a ga of 34 to 42 weeks ( n=290  355 ) . we excluded patients with unknown sex determination ( n=14 ) , congenital heart disease ( n=764 ) and other major congenital defects ( n=1574 ) . to avoid confusion with other conditions that may present with respiratory distress at birth , we excluded infants with a diagnosis of meconium aspiration syndrome ( n=1950 ) or culture - positive sepsis in the 1 four days of life ( n=195 ) . case definition was based on vermont oxford network criteria for rds ( impairment in oxygenation and a chest radiograph consistent with rds ) , or surfactant administration . ga was entered as completed weeks of gestation from the obstetrical medical record and was based on last menstrual period , and was confirmed or modified by fetal ultrasound . we classified infants as small for ga , appropriate for ga or large for ga based on birth weight and ga in comparison with the 10 and 90 percentiles of fenton growth curves . we determined mode of delivery ( vaginal versus cesarean section ) from maternal the international classification of diseases-9 revision procedure codes and the infant 's medical record . data regarding indications for cesarean section delivery was not available to be collected for analysis . we assigned multiplicity of gestation ( singleton versus higher - order ) based on infants ' sharing the same maternal medical record number and maternal admission date to labor and delivery . we created a combined race / ethnicity designation by first classifying subjects ' ethnicity as hispanic or non - hispanic . we further subdivided non - hispanic subjects according to race into white , black , asian and american indian / eskimo . parents could designate race as other if they did not identify with any of these discrete designations . if race / ethnicity was not recorded , the infant 's race / ethnicity was assigned as unknown . we assigned maternal diagnoses of diabetes ( including gestational ) ( 250 to 250.9 ; 648.0 to 638.04 ; 775 ) , pre - eclampsia / eclampsia ( 642.4 to 642.63 ) , chorioamnionitis ( 658.4 to 658.43 ; 762.7 ) , and prolonged rupture of membranes ( 658.2 to 658.23 ) based on the international classification of diseases-9 revision diagnosis codes . we extracted the use of surfactant and mechanical ventilation from each infant 's medical record . we compared demographic characteristics of infants with and without rds using -tests and the mann - whitney test , when appropriate . we created a multivariate logistic regression model with rds as the dependent variable , and sex , race / ethnicity , ga , size for ga , mode of delivery , multiplicity of gestation , pre - eclampsia / eclampsia , maternal diabetes , chorioamnionitis and prolonged rupture of membranes as predictor variables . we chose variables on the basis of prior studies of risk factors for rds in lower ga populations . data from a subgroup of infants admitted to a level iii neonatal intensive care unit ( 6.43% of the cohort ) included antenatal glucocorticoid administration and permitted analysis of differential administration by race / ethnicity and sex . we calculated odds ratios for each predictor variable along with 95% confidence intervals and tested hypotheses using a two - sided =0.05 . to explore effects of interactions of race or ga with sex on the risk for rds , we calculated race- and ga - specific odds ratios , adjusting for size for ga , mode of delivery , multiplicity of gestation pre - eclampsia / eclampsia and maternal diabetes . we conducted all analyses using stata v.9.2 ( statacorp lp , college station , tx , usa ) . the overall incidence of rds in this cohort was 0.31% ( n=895 ) , with incidence in late preterm infants of 3.22% and in term infants of 0.12% . infants with rds were more likely to be male , white , of lower ga and delivered by cesarean section . our data analysis showed rds infants to be either sga or lga . among infants with rds , 44.8% required mechanical ventilation and 38.9% received surfactant ( table 1 ) . to characterize the relationships among ga , sex , and race / ethnicity and the absolute risk of rds , we plotted the crude incidence of rds by ga for each race and sex category ( figure 1 ) . at 34 weeks of ga , white males had the highest risk of rds ( 13.0% ) , whereas hispanic females had the lowest risk of rds ( 4.3% ) . in each race / ethnicity and sex category , risk for rds decreased with increasing ga until 37 weeks of gestation . regardless of race / ethnicity , females had a lower incidence of rds than males . in whites , the absolute risk difference between males and females persisted until approximately 38 weeks of ga . however , the difference decreased with advancing ga . in the other race / ethnicity categories , we observed no consistent differences between males and females after 34 weeks ga , except for an unexplained large difference between asian males and females at 35 weeks ( 0.7% in females and 3.5% in males ) . in the multivariate logistic regression model , ga was the strongest predictor of rds ( table 2 ) . compared with infants born at 40 weeks ga , those born at 34 weeks ga had an adjusted odds ratio ( aor ) for rds of 114.12 ( 95% confidence interval 84.71 to 153.74 ) . even infants born at 38 weeks gestation had a greater risk of rds ( aor 1.67 ; 95% confidence interval 1.16 to 2.41 ) . after adjusting for other covariables , males still had a greater risk of rds than females ( aor 1.68 ; 95% confidence interval 1.45 to 1.93 ) . consistent with previously reported racial / ethnic risk differences for rds among infants born at < 32 weeks gestation , we found blacks had a lower risk of rds than whites . as our cohort had a large proportion of hispanics ( 25% ) and asians ( 20% ) , we were able to evaluate their risk of rds compared with non - hispanic whites , and found both asians and hispanics to be at lower risk for rds ( table 2 ) . additional significant independent predictors of rds in the multivariate regression were caesarean delivery , maternal diabetes and chorioamnionitis . multiple gestation , maternal pre - eclampsia and prolonged rupture of membranes were significant protective factors . we also developed ga- and race / ethnicity - specific regression models ( figure 2 ) . for gas < 39 weeks , males had a higher risk of rds compared with females ( point estimates for the aor of 1.2 to 2.2 ) . after 39 weeks , the point estimates still showed males at increased risk but were not statistically significant . for race / ethnicity , males were at a statistically increased risk for rds compared with females in whites , asians and hispanics . we evaluated a potentially confounding association between maternal antenatal corticosteroid administration and either race / ethnicity or sex by comparing a subgroup of male and female infants admitted to a level iii neonatal intensive care unit for whom data on maternal antenatal corticosteroid administration were available ( n=1015 ) . in this subgroup , 5.35% of males and 5.72% of females were born to mothers who received antenatal corticosteroids (  
 p value=0.28 ) . in addition , using pairwise comparisons , we found that the only significant difference occurred between asians ( 4.62% ) and blacks ( 6.25% ) (  
 p value=0.009 ) who had similar rates of rds . differential administration of antenatal corticosteroids by sex or race / ethnicity does not appear to have confounded the overall analysis . our findings confirm and extend a recent , large population - based european cohort study of rds risk factors , and are consistent with prior studies that found increased risk of rds by week through 39 weeks of gestation . these findings illustrate the importance of each week of gestation for rds risk reduction through 39 weeks gestation . we also found that the increased risk of rds associated with male sex and white race / ethnicity observed in preterm infants persists in late preterm and term infants . differences in hormonal regulation of lung development provide candidate mechanisms to account for an increased risk of rds associated with male sex . the racial disparity in risk of rds between whites and blacks previously observed in infants < 32 weeks ga also persists in late preterm and term infants . the composition of our cohort permitted demonstration of increased rds risk in white infants versus both asian and hispanic infants . the mechanisms that account for these differences require further investigation and replication in other cohorts . these findings contrast with those of studies that have not shown lower rates of rds among asian infants , and may reflect admixture in the california asian population . hispanics in northern california are also an ethnically heterogeneous group associated with admixture with european , african , and indigenous american populations . on the basis of the low frequency of medi - cal insurance in our cohort ( < 5% compared with 47% in the general population in california ) , although the size of our cohort provides adequate statistical power to observe the difference in rds risk in male versus female infants and between infants of different races / ethnicities , our study has several limitations . first , although maternal and neonatal data were collected prospectively , our analysis was retrospective and therefore , we did not have complete data for the entire cohort on antenatal steroids . however , subgroup analysis suggested that differential antenatal corticosteroid administration did not account for sex and race / ethnicity differences in rds risk . to reduce misclassification , we repeated our multivariate analysis using a more restrictive definition of rds ( only infants who received surfactant ) . males remained at a greater risk of rds than females ( aor 1.75 ; 95% confidence interval 1.39 to 2.20 ) . asians were still at a lower risk of rds than whites ( aor 0.54 ; 95% confidence interval 0.39 to 0.74 ) . although not statistically significant , there was trend for hispanics ( aor 0.83 ; 95% confidence interval 0.63 to 1.08 ) and blacks ( aor 0.70 ; 95% confidence interval 0.46 to 1.06 ) to have a decreased risk of rds compared with whites . the reduced number of cases with the more restrictive definition of rds diminished our ability to find statistical differences . third , although it is unlikely that changes in frequency of use of inhaled nitric oxide that occurred during the 9-year interval of cohort accumulation impacted rds risk , other unrecognized practice changes may have confounded our analysis . despite these limitations , our study suggests that decisions concerning timing of delivery should acknowledge rds risk associated with male sex and white race / ethnicity in late preterm and term infants . for example , because cesarean delivery on maternal request prompts 4 to 18% of the 1  000  000 cesarean sections annually in the united states , counseling for women to avoid elective delivery before 39 completed weeks of gestation should also include acknowledgement of rds risk associated with male sex and white race / ethnicity . in conclusion , our study shows that male sex and white race / ethnicity are independent risk factors for rds in late preterm and term infants . future studies to elucidate mechanisms that account for this differential risk will inform obstetrical counseling and decision - making .
objective : to determine whether race / ethnicity and sex independently increase risk of respiratory distress syndrome ( rds ) in late preterm and term infants.study design : using a cohort design , we studied the risk of rds associated with race / ethnicity and sex in infants with gestational age ( ga ) 34 to 42 weeks born between 1 january 2000 and 31 december 2009 ( n=286  454 ) within 12 hospitals in the northern california kaiser permanente medical care program.result:male sex ( adjusted odds ratio ( aor ) 1.68 ; 95% confidence interval 1.45 to 1.93 ) and white race / ethnicity ( vs asians ( aor 0.57 ; 95% confidence interval 0.47 to 0.70 ) , blacks ( aor 0.66 ; 95% confidence interval 0.50 to 0.87 ) , and hispanics ( aor 0.76 ; 95% confidence interval 0.64 to 0.90 ) ) independently increase risk for rds regardless of ga . 
 a ga < 39 weeks , operative delivery , maternal diabetes , and chorioamnionitis also increased rds risk in this cohort.conclusion:male sex and white race / ethnicity independently increase risk for rds in late preterm and term infants . 
 timing of elective delivery should acknowledge these risks .