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The objective of the study was to determine the relationship between nighttime delivery and neonatal encephalopathy (NE).
The design of the study was a retrospective population-based cohort of 1,864,766 newborns at a gestation of 36 weeks or longer in California, 1999-2002. We determined the risk of NE associated with nighttime delivery (7:00 pm to 6:59 am).
Two thousand one hundred thirty-one patients had NE (incidence 1.1 per 1000 births). Nighttime delivery was associated with increased NE (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.03–1.20), birth asphyxia (OR, 1.18; 95% CI, 1.08–1.29), and neonatal seizures (OR, 1.17; 95% CI, 1.07–1.28). In adjusted analyses, nighttime delivery was an independent risk factor for NE (OR, 1.10; 95% CI, 1.01–1.21), as were severe intrauterine growth retardation (OR, 3.8; 95% CI, 3.1–4.8); no prenatal care (OR, 2.0; 95% CI, 1.4–2.9); primiparity (OR, 1.5; 95% CI, 1.4–1.7); advanced maternal age (OR, 1.3; 95% CI, 1.16–1.45); and infant male sex (OR, 1.3; 95% CI, 1.2–1.4).
Future studies of time of delivery may generate new strategies to reduce the burden of NE.
It is thus assumed that some cases of NE could be prevented with improved quality of care. However, the strength of the relationship between quality of care and NE is unknown, especially given that intrapartum complications are absent in the vast majority of infants with NE.
During the months of July and August, teaching hospitals frequently employ house officers who have just recently completed their medical education and are thus less experienced. Two studies in England have reported higher intrapartum death rates in the summer.
There are no recent studies of the relationship between weekend delivery and neonatal outcome in the United States. Whether neonatal outcomes differ in teaching and nonteaching hospitals during the summer months has also not been evaluated to our knowledge. The relationship between the time of delivery and the incidence of NE in term infants has not been studied previously. In a recent California population, we examined the association between NE and factors that have potential implications for quality of care, including hour, day, and month of delivery.
Materials and Methods
We examined a population-based retrospective cohort using the California-linked birth infant death file created specifically to study perinatal outcomes.
The data set contains information from birth and death certificates linked to state-wide hospital discharge data for mother and infant. We included all infants born in California at a gestation of 36 weeks or longer (term gestation), from Jan. 1, 1999, to Dec. 31, 2002. In this population, we identified infants with NE by searching hospital discharge diagnoses. Infants with extreme birth weights (<1500 g or >5500 g) or maternal ages (<12 or >55 years) were excluded from the study, as were infants with missing data regarding hour of birth.
Neonatal encephalopathy was our primary outcome of interest. Because NE represents a broadly characterized and nonspecific disorder, we attempted to limit heterogeneity by focusing on more severe cases. To be categorized as having NE, a newborn infant had to meet at least 1 of the following birth hospitalization discharge diagnostic criteria:
Severe birth asphyxia (International Classification of Diseases, Ninth Revision [ICD-9-CM] code 768.5).
Neonatal seizure (codes 779.0, 345-345.9, and 780.3).
Mechanical ventilation (code 96.70, 96.71 or 96.72) associated with any of the following diagnoses suggestive of NE:
birth asphyxia (codes 768.5, 768.6, and 768.9); neonatal seizures (codes 779.0, 345-345.9, and 780.3); cerebral irritability or central nervous system depression (codes 779.1 and 779.2); hypotonia or other perinatal conditions (codes 779.8 and 779.9); fetal distress associated with infant morbidity (codes 768.2-768.4); birth trauma or encephalopathy resulting from birth injury (codes 767.8 and 767.9); intrapartum anoxia or brain hemorrhage resulting from birth trauma (code 767.0); congenital encephalopathy or unspecified anomaly of nervous system (code 742.9); or anoxia or encephalopathy (code 348.1 and 348.3).
Neonatal death (within 28 days of delivery) associated with any of the diagnoses listed in the previous text.
Given the heterogeneity of the term NE, we also studied the relationship between time of delivery and birth asphyxia (codes 768.5, 768.6, or 768.9), as well as the relationship between time of birth and neonatal seizures (codes 779.0, 345-345.9, or 780.3).
The hour of delivery, our primary predictor of interest, was obtained from birth certificate data. Based on previous literature,
we defined a priori the daytime as spanning from 7:00 am to 6:59 pm and nighttime as the period from 7:00 pm to 6:59 am. Weekend (Saturday or Sunday) and summer (July and August) deliveries were determined from hospital discharge abstracts. Hospitals were designated into 1 of the following 3 categories according to the California Office of Statewide Health Planning and Development Hospital Annual Financial Data: teaching hospitals; rural hospitals (designated by the state as being either rural or small); or nonteaching, nonrural hospitals.
We examined the following covariates obtained from birth certificates: maternal age, ethnicity, and education; lack of prenatal care; parity; infant sex; gestational age; and multiple gestation. The source of payment for the birth admission was used as an indicator of socioeconomic status (SES). High SES consisted of patients with private insurance or health maintenance organization coverage, and low SES included those who were indigent, self-pay, or who had Medicaid or Medicare. Intrauterine growth restriction (IUGR) was defined as mild (birthweight <10% for gestational age), moderate (<5%), or severe (<1%),
based on ethnicity and sex-specific normative data compiled from the entire study population.
The association between hour of birth and NE was determined by calculating univariate and multivariable odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. To control for case mix, we included in our multivariable model all factors that had a significance level of P < .10 in the univariate analysis: mother's race and age; infant sex; lack of prenatal care; primiparity; gestational age (36 weeks, 37-41 weeks, ≥42 weeks); intrauterine growth retardation (birthweight <1% for gestational age), and type of hospital.
All statistical analyses were performed with SAS (version 9.1; SAS Institute, Cary, NC). No personal identifiers were available in the datasets examined. This study received approval from the institutional review boards at the University of California, San Francisco, the Office of Statewide Health Planning and Development, and the California State Department of Health.
Of 1,864,766 term infants in the study population, 2131 had NE, providing a population incidence of 1.1 per 1000 term live births. The incidence of NE remained unchanged during the study years. Sixteen percent of NE cases resulted in neonatal death prior to 1 month of age. The rate of neonatal mortality associated with NE (0.18 per 1000 term births) remained unchanged during the study period. Of all neonatal deaths that occurred in the birth cohort, 20.8% met inclusion criteria for NE.
Approximately one-third of all infants (32.8%) were delivered at night, and 22.8% were delivered during the weekend. Nighttime delivery was associated with an increase in risk of NE (OR, 1.13; 95% CI, 1.03–1.2). Risk of NE did not vary significantly for weekend or summer deliveries (Table 1). However, being delivered either at a teaching (OR, 1.9; 95% CI, 1.7–2.1) or rural (OR, 1.4; 95% CI, 1.2–1.7) hospital was associated with increased risk of NE when compared with nonteaching, nonrural hospitals.
TABLE 1Univariate risk factors for NE among 1,864,766 infants born in California, 1999-2002
Time of delivery
Type of hospital
Maternal age, y
Elementary or middle school
Lower socioeconomic status
No prenatal care
Gestational age, wks
RR, relative risk.
Wu. Nighttime delivery and neonatal encephalopathy. Am J Obstet Gynecol 2011.
The risk of NE during the night was highest during the period between 10:00 pm and 4:00 am (Figure). During these hours, the incidence of NE was 1.33 per 1000 term births, which was significantly higher than the rate of NE among daytime deliveries (OR, 1.22; 95% CI, 1.10–1.36). In contrast, births occurring in the early evening (7:00-10:00 PM) and during the early morning (4:00-7:00 am) were no different from daytime deliveries with respect to risk of NE (P > .05).
After adjusting for potential confounders (Table 2), nighttime delivery remained an independent risk factor for NE (OR, 1.10; 95% CI, 1.01–1.21). Both teaching (OR, 1.8; 95% CI, 1.6–2.0) and rural hospitals (OR, 1.4; 95% CI, 1.1–1.7) also demonstrated an increased adjusted risk of NE when compared with nonteaching, nonrural hospitals. Infant and maternal characteristics independently associated with an elevated risk of NE were severe IUGR (OR, 4.1; 95% CI, 3.3–5.0); no prenatal care (OR, 2.0, 95% CI, 1.4–2.9); gestation of 36 weeks (OR, 1.9; 95% CI, 1.6–2.2) or gestation of 42 weeks or longer (OR, 1.3; 95% CI, 1.1–1.5) when compared with 37-41 weeks; primiparity (OR, 1.5; 95% CI, 1.4–1.7); maternal age 35 years old or older compared with 19-34 years (OR, 1.3; 95% CI, 1.2–1.5) and infant male sex (OR, 1.3; 95% CI, 1.2–1.4). Changing maternal age to a continuous variable did not substantively alter these findings. In contrast, after adjusting for confounders, both Hispanic (OR, 0.8; 95% CI, 0.7–0.9) and Asian (OR, 0.7; 95% CI, 0.6–0.8) maternal ethnicities exhibited a decreased risk of NE when compared with whites.
In multivariable analyses restricted to specific subcategories of NE, we found that nighttime delivery also increased the risk of birth asphyxia (OR, 1.18; 95% CI, 1.08–1.29) and neonatal seizures (OR, 1.17; 95% CI, 1.07–1.28).
Risk of NE was significantly elevated in babies born at night to primiparous women (OR, 1.21; 95% CI, 1.07–1.37) but not in babies born at night to multiparous women (OR, 1.02; 95% CI, 0.89–1.16). The difference between these 2 ORs was statistically significant (P = .05). The risk of NE associated with nighttime deliveries also differed by race. Unlike whites (OR, 1.26; 95% CI, 1.09–1.45), Hispanics demonstrated no evidence of a nighttime birth disadvantage (OR, 1.00; 95% CI, 0.88–1.15; P = .02 for the difference). There were no interactions between nighttime and weekend delivery and between nighttime and summer delivery (P > .10).
The risk of NE remained unchanged during the summer months when compared with the rest of the year, both in teaching (OR, 1.06; 95% CI, 0.73–1.54) and in nonteaching hospitals (OR, 1.00; 95% CI, 0.83–1.17).
We identified infants born by elective cesarean section using a set of ICD-9-CM diagnostic and procedure codes that have been validated by chart review to indicate an elective cesarean delivery.
When these deliveries were excluded, nighttime delivery remained a significant predictor of NE in multivariable analysis (OR, 1.13; 95% CI, 1.01–1.25).
If one assumes that the association between nighttime delivery and NE is causal, the population attributable risk of nighttime birth for NE in our population is 4.1%.
In a large contemporary cohort of term infants, we found that the odds of NE was 10% higher following a nighttime delivery after adjusting for potential confounding factors. This elevated risk was greatest (22%) during the hours of 10:00 pm to 4:00 am. Delivery at night was similarly associated with an 18% increased odds of being diagnosed with birth asphyxia and a 17% increased chance of having neonatal seizures.
There are several possible explanations for the association between nighttime delivery and NE. Investigators have suggested that the level of medical care may decrease during the night, producing a “circadian rhythm of quality of care.”
Thus, the relationship between time of delivery, quality of care, and neonatal outcomes deserves further study.
Another possible explanation for the daytime birth advantage is that planned cesarean deliveries occur more often during the day. However, we found that the increased risk of NE persisted when elective cesarean deliveries were excluded from analysis. Alternatively, infants who are delivered at night may have an inherently higher risk of NE because of unmeasured biological factors. Although we attempted to adjust for case mix by including in our multivariable model a variety of known risk factors for NE, there may be other factors such as diurnal variations in maternal and fetal hormone levels that could have an impact on the risk of NE.
During the summer months (July and August), teaching hospitals frequently employ house officers who are relatively inexperienced. If quality of care were subsequently compromised during these months, the risk of NE might vary more dramatically in the summer within teaching hospitals. In contrast, we found that infants born during the summer in both teaching and nonteaching hospitals exhibited the same risk of NE as infants born during other times of the year.
Our finding that maternal primiparity increases the risk of NE by 51% confirms previous reports.
However, studies addressing time of birth and pregnancy outcomes have rarely examined the effect of parity. We found that the adverse effect of nighttime delivery on NE was only evident in infants born to primiparous women, whereas multiparous women were just as likely to deliver an infant with NE during the day as during the night. Primiparous women are more likely to suffer from prolonged labor, and prolonged labor is more common among nighttime deliveries.
This could potentially explain the increased risk of NE seen in primiparous women who deliver at night. Alternatively, primiparous women may be more sensitive to factors that have a negative impact on the quality of care and thus be more likely to respond to targeted interventions.
Intrauterine growth restriction represented the strongest risk factor for NE among the factors examined in our study, confirming similar findings in previous population studies.
Teaching hospitals and rural hospitals exhibited an 87% and 41% increased risk of NE, respectively, when compared with nonteaching, nonrural hospitals. Hospital variation in case mix, with sicker and more complicated patients being treated at teaching hospitals, is the most likely explanation for these findings. Whether quality of care differences between academic and nonacademic centers could also contribute to these differences is unknown. The decreased incidence of NE among Hispanics and Asians in our study is consistent with the lower infant mortality rates previously observed in Latina and Asian American women when compared with whites.
It is unclear whether these ethnic differences are because of genetic, social, or other factors.
Neonatal encephalopathy is a heterogeneous clinical syndrome, and there are no validated diagnostic codes for NE. Given the lack of consensus regarding the use of the terms NE and birth asphyxia and the lack of clarity regarding the underlying cause of NE in most cases, we chose to define NE broadly, to include all identified cases of infants with severe newborn brain dysfunction. In addition to the all-inclusive diagnosis of NE, we also studied birth asphyxia and neonatal seizures (subcategories of NE) and found a similar increased risk among infants born at night.
Our study has important limitations. As in all studies that rely on administrative data, our analyses are susceptible to inaccuracies in diagnostic coding; however, assuming coding errors are nondifferential with respect to time of birth, the errors would result in a conservative bias. We also lack potentially important information regarding obstetrical interventions and complications that may confound or explain the relationship between time of birth and NE. No information was available regarding staffing levels or differing levels of expertise among the medical caregivers. Advantages of our study include the large population-based setting, the ethnic diversity, and the multiple outcome measures that could be analyzed, all of which point toward an association between time of birth and NE. Future studies of time of delivery and quality of care may generate new strategies to help reduce the burden of neonatal encephalopathy and its often devastating neurological consequences.
We would like to thank Nancy Hills for her assistance with data analysis.