Asphyxia, Neurologic Morbidity, and Perinatal Mortality in Early-Term and Postterm Birth
BACKGROUND AND OBJECTIVES: Neonatal outcomes vary by gestational age. We evaluated the association of early-term, full-term, and postterm birth with asphyxia, neurologic morbidity, and perinatal mortality.
METHODS: Our register-based study used retrospective data on 214 465 early-term (37+0–38+6 gestational weeks), 859 827 full-term (39+0–41+6), and 55 189 postterm (≥42+0) live-born singletons during 1989–2008 in Finland. Asphyxia parameters were umbilical cord pH and Apgar score at 1 and 5 minutes. Neurologic morbidity outcome measures were cerebral palsy (CP), epilepsy, intellectual disability, and sensorineural defects diagnosed by the age of 4 years. Newborns with major congenital anomalies were excluded from perinatal deaths.
RESULTS: Multivariate analysis showed that, compared with full-term pregnancies, early-term birth increased the risk for low Apgar score (<4) at 1 and 5 minutes (odds ratio 1.03, 95% confidence interval 1.03–1.04 and 1.24, 1.04–1.49, respectively), CP (1.40, 1.27–1.55), epilepsy (1.14, 1.06–1.23), intellectual disability (1.39, 1.27–1.53), sensorineural defects (1.24, 1.17–1.31), and perinatal mortality (2.40, 2.14–2.69), but risk for low umbilical artery pH ≤7.10 was decreased (0.83, 0.79–0.87). Postterm birth increased the risk for low Apgar score (<4) at 1 minute (1.26, 1.26–1.26) and 5 minutes (1.80, 1.43–2.34), low umbilical artery pH ≤7.10 (1.26, 1.19–1.34), and intellectual disability (1.19, 1.00–1.43), whereas risks for CP (1.03, 0.84–1.26), epilepsy (1.00, 0.87–1.15), sensorineural defects (0.96, 0.86–1.07), and perinatal mortality (0.91, 0.69–1.22) were not increased.
CONCLUSIONS: Early-term birth was associated with low Apgar score, increased neurologic morbidity, and perinatal mortality. Asphyxia and intellectual disability were more common among postterm births, but general neurologic morbidity and perinatal mortality were not increased.
- CI —
- confidence interval
- CP —
- cerebral palsy
- GW —
- gestational weeks
- HDR —
- Hospital Discharge Register
- ICD —
- International Classification of Diseases
- MAS —
- meconium aspiration syndrome
- MBR —
- Finnish Medical Birth Register
- OR —
- odds ratio
- THL —
- National Institute for Health and Welfare
What’s Known on This Subject:
Postterm birth is generally associated with higher risk for perinatal morbidity and mortality, and long-term neurologic sequelae. The rate of postterm birth decreases, while the rate of early-term birth increases. Only recently, risks related to early-term birth have been recognized.
What This Study Adds:
Postterm birth causes a higher risk of birth asphyxia, but general long-term neurologic morbidity is comparable with full-term birth. Among children born early-term, risks for low Apgar score and long-term neurologic morbidity are increased.
Pregnancy outcomes vary by gestational age at birth. Earlier studies have mainly concentrated on complications of preterm or postterm birth, defined as birth at <37 or ≥42+0 gestational weeks (GW).1 Term births (at 37+0–41+6 GW) have usually been considered homogeneous low-risk occasions, and early-term births (at 37+0–38+6 GW) have often been included in reference groups.
Early-term birth occurs in 18% to 29% of pregnancies,2,3 and the incidence seems to be rising.4 Recent evidence shows an association of early-term birth with increased short-term and long-term morbidity.3,5–7 Postterm birth, in turn, occurs in ∼5% of pregnancies, varying from 0.4% to 8.1% in European and North American countries. This variation is mostly due to different obstetric management protocols. The proportion of postterm birth seems to be decreasing.8 Elevated risk for perinatal mortality and morbidity is associated with postterm birth.9–11
In Finland, the rate of early-term birth is 17% to 18% and the rate of postterm birth is 4% to 5%.12 Our population-based study evaluated birth asphyxia, long-term neurologic morbidity, and perinatal mortality in relation to gestational age in term and postterm birth.
The Finnish Medical Birth Register (MBR), maintained by the National Institute for Health and Welfare (THL), provided the data. The MBR collects baseline data on pregnancies, deliveries, and the newborn’s outcome during the first days of life. It collects data on all live births and stillbirths beginning from 22+0 GW and/or birth weight at least 500 g in Finland. The MBR data are compiled at the time of birth, by using the mother’s prenatal charts as a data source. Fewer than 0.1% of all newborns are missing from the MBR, but basic information on missing cases is routinely obtained from the Central Population Register (live births) and the Cause of Death Register (stillbirths and neonatal deaths). Following these linkages, the MBR is complete. Data on diagnoses related to pregnancies and deliveries, and children’s diagnoses until the age of 4 years, were collected from the Hospital Discharge Register (HDR), which contains nationwide linkable data on all inpatient hospital discharges and is maintained by the THL.
The study population comprised women with singleton term and postterm deliveries and their newborns between 1989 and 2008. There were 1 138 109 births, of which 7230 (0.6%) were excluded due to unknown gestational age at birth. Stillbirths were excluded from all analyses except for perinatal mortality. Thus, live births numbered 1 129 481. In Finland during the study period, gestational age was determined either by date of the mother’s last menstrual period, mostly during the earlier years, or by first-trimester ultrasonography. In this study, births were divided into subgroups as follows: early-term 37+0–38+6 GW, full-term 39+0–41+6 GW, and postterm ≥42+0 GW. The study was divided into 5-year periods as follows: 1989–1993, 1994–1998, 1999–2003, and 2004–2008.
The main outcomes included early asphyxia-related morbidity, long-term neurologic morbidity, and perinatal mortality. Neonatal asphyxia parameters assessed were Apgar score <4 at 1 and 5 minutes, umbilical artery pH below 7.00 and 7.10, and meconium aspiration syndrome (MAS). Data on Apgar score at 1 minute were available for all newborns during the whole study period. Data on Apgar score at 5 minutes were reported in the MBR only since 2004 (comprising 230 408 [83.8%] births). Data on umbilical artery pH were included in the MBR in 1990, and were available for 519 210 (45.9%) births. MAS was defined as the presence of meconium in both amniotic fluid and neonatal trachea, chest radiograms showing massive bilateral patchy infiltrates of the lung, and frequently pleural fluid effusions.13 The International Classification of Diseases (ICD) codes identifying MAS are shown in Fig 1.
Long-term neurologic morbidity consisted of cerebral palsy (CP), epilepsy, intellectual disability, and sensorineural defects, including visual impairment and deafness, at the age of 4 years. All inpatient and outpatient visits due to CP, epilepsy, intellectual disability, and sensorineural defects diagnoses registered in public hospitals were collected from the HDR. Only occasional children treated in private hospitals and children who emigrated before diagnoses were established are missing from the HDR. In Finland, the diagnosis of CP, epilepsy, intellectual disability, and sensorineural defects is based on medical history, ultrasonography, and MRI data as required, and multidisciplinary evaluations in secondary or tertiary pediatric neurology units. CP is usually evident within the first 2 years of life and practically always by the age of 3 to 4 years.7 The diagnosis of CP is added to the HDR immediately after establishment. The Finnish public health care system calls for all children to undergo annual physical examinations; thus, the neurologic diagnoses are consistently recognized by the age of 4 years. A neurologic disorder at 4 years was recorded in the study if the child was detected in the HDR with ICD-9 (1989–1995) and ICD-10 (1996–2008) codes for neurologic diagnoses (Fig 1). All the data linkages were performed by using unique personal identity codes anonymized by the authorities.
Perinatal deaths included stillbirths and early neonatal deaths during the first 7 days of life, and analyses were performed after excluding newborns with major congenital anomalies according to the Register on Congenital Malformations, retained by THL. Perinatal mortality and early neonatal deaths were analyzed in relation to the total number of births in the same gestational week. Data on stillbirths, coded in the MBR by using the ICD codes in Fig 1, were further correlated with the numbers of ongoing pregnancies in the beginning of the particular gestational week.
THL, as a register keeper, gave the necessary authorization required by national data protection legislation (THL/1200/5.05.00/2012).
Characteristics of the newborns and their mothers are given as means with SDs in case of normally distributed continuous variables, by medians with interquartile range in skewed distributed variables, and by number of values as percentages if variables were categorical. Gestational age groups were compared by using the Mann-Whitney test or the χ2 test, when appropriate. The following variables, collected from the MBR, were used to study the risk factors for neonatal asphyxia and neurologic adverse outcome by logistic regression analyses using multivariate models: in vitro fertilization, smoking, parity, maternal age (<20, 20–34, and ≥35 years), delivery induction, mode of delivery (vacuum extraction, planned cesarean delivery, emergency cesarean delivery, vaginal breech delivery), early- or postterm birth, gender, birth weight <2500 g or ≥4000 g, birth weight adjusted for gestational age (small for gestational age [<–2 SD] and large for gestational age [>+2 SD], according to the gender-specific national standard14), and MAS. Low pH (<7.00 and 7.00–7.10), and Apgar score <4 at 1 and 5 minutes were included in the analysis of neurologic outcome. Results are shown as odds ratios (ORs) with 95% confidence intervals (CIs) in modeling risk factors for adverse neonatal outcomes. Statistical analyses were performed on IBM SPSS Statistics version 20.0 (IBM SPSS Statistics, IBM Corporation, Chicago, IL) or SAS version 9.3 (SAS Institute, Inc, Cary, NC); P < .05 was considered statistically significant.
The study population comprised 1 129 481 live births, with 214 465 (19%) early-term and 55 189 (4.9%) postterm births. Characteristics of mothers and newborns are shown in Table 1. Delivery induction was more common in both early- and postterm birth than in full-term birth (OR 1.12, 95% CI 1.11–1.14 and OR 6.30, 95% CI 6.19–6.42, respectively). Delivery induction was not associated with CP (Table 2). Likewise, the rate of emergency cesarean delivery was increased in early- and postterm birth (OR 1.40, 95% CI 1.37–1.42, and OR 2.31, 95% CI 2.25–2.36, respectively).
The incidences of low Apgar score at 1 and 5 minutes, and low umbilical artery pH ≤7.10 are shown in Fig 2. By logistic regression analysis, early-term birth was an independent risk factor for low Apgar score at 1 and 5 minutes (OR 1.03, 95% CI 1.03–1.04, and OR 1.24, 95% CI 1.04–1.49, respectively). Similarly, postterm birth was an independent risk factor for low Apgar score at 1 and 5 minutes (OR 1.26, 95% CI 1.26–1.26, and OR 1.80, 95% CI 1.43–2.34, respectively). Low Apgar score at 1 and 5 minutes was associated with CP, epilepsy, intellectual disability, and sensorineural defects (Table 2).
Early-term birth was not associated with umbilical artery pH ≤7.10 or pH <7.00 (OR 0.83, 95% CI 0.79–0.87, and OR 1.06, 95% CI 0.96–1.18, respectively). In contrast, postterm birth was an independent risk factor for low umbilical artery pH (pH ≤7.10, OR 1.26, 95% CI 1.19–1.34, and pH <7.00, OR 1.18, 95% CI 1.02–1.37, respectively). Umbilical artery pH <7.00 increased risk for CP, epilepsy, intellectual disability, and sensorineural defects (Table 2). Both low Apgar score <4 at 1 minute and low umbilical artery pH <7.10 occurred in 14.0% of early-term births and 8.8% of postterm births (P = .389).
MAS was more common in postterm than in full-term pregnancies (OR 3.20, 95% CI 3.20–4.16). MAS was associated with intellectual disability, but not with CP or epilepsy (Table 2).
Data on long-term neurologic impairments are shown in Table 3. In multivariate analysis, early-term birth was identified as a risk factor for CP, epilepsy, intellectual disability, and sensorineural defects. Postterm birth was an independent risk for intellectual disability, but not for CP, epilepsy, or sensorineural defects (Table 2). The incidence of CP decreased over the study period (P < .001). At the same time, the incidences of epilepsy, intellectual disability, and sensorineural defects increased (P < .001 for all) (Table 3).
Excluding newborns with major congenital anomalies, total perinatal mortality of the study population was 1.3 per 1000 births. The incidence was highest among early-term births: 2.5 deaths per 1000 births. In full-term birth the incidence was 1.0 per 1000 and in postterm birth 0.9 per 1000. Increased risk for early neonatal death was observed among early-term and postterm births, as compared with full-term birth (Table 4). The risk for stillbirth, as compared with ongoing pregnancies, was decreased in both early-term and postterm births (Table 4). Perinatal mortality decreased during the study period due to decreased stillbirth rate (P < .001), but the decrease in early neonatal death rate was not statistically significant (P = .071) (Fig 3).
We demonstrated that early-term birth is associated with increased risk for perinatal mortality and neurologic morbidity as compared with full-term and postterm birth. We also confirmed that postterm birth elevates risk for primary asphyxia as measured by low umbilical artery pH and low Apgar score. Among children born postterm, however, perinatal mortality or neurologic morbidity, including CP, epilepsy, and sensorineural defects, were not more common, whereas intellectual disability was.
The rate of elective induction of delivery after 41 GW or even in the early-term period is increasing in many countries,15 but in Finland such routine inductions have been less frequent.8 Despite an increasing overall number of delivery inductions,12 the rate of early-term birth did not vary substantially, and the rate of postterm birth increased during the 20-year study period. Nevertheless, the incidences of perinatal mortality and long-term morbidity in our study population were comparable with those in earlier studies.9,10,16,17 We did not find the controversial association of delivery induction with CP.18,19
In term deliveries, low Apgar score at 5 and 10 minutes frequently reflects perinatal asphyxia and acidosis, and predicts neonatal morbidity and mortality.20–22 Here, as in previous studies,10,23 both postterm and early-term birth led to increased risk for low Apgar score, known to associate with long-term neurologic disability, decreased cognitive function,24 epilepsy,25 and CP.21 In our study, the strongest risk factor for neurologic morbidity was low Apgar score at 1 minute, possibly explained by limitations in recording Apgar score at 5 minutes in the MBR.
Neonatal mortality and neurologic morbidity associate with low umbilical artery pH at birth.26 The mean umbilical artery pH tends to decrease, and acidosis tends to increase, with advancing gestational age also in a low-risk population.11,27 In line with earlier findings,3 early-term birth was not associated with low pH. In contrast, postterm birth was an independent risk factor for low umbilical artery pH. Postterm birth, however, did not raise the risk for long-term neurologic sequelae, as did early-term birth. Such difference in outcomes may be explained by increased vulnerability of early-term newborns due to relative physiologic immaturity.3
Children born postterm are assumed to be at risk for neurologic complications and developmental aberrations.27,28 The association of CP with postterm birth has been controversial in earlier studies with early-term births often included in their reference groups.7,29 A U-shaped pattern exists in risk for CP among term newborns, with the highest risk at 37 GW and at 42 GW and beyond.7 Interestingly, we found the highest risk for CP at early-term, whereas postterm birth did not show a higher risk. One study reported an association of epilepsy with postterm birth.30 Conversely, we found that postterm birth did not lead to increased risk for epilepsy or sensorineural defects, whereas early-term birth did. Lower IQ occurs in early-term and postterm birth, with the highest IQ at term.31,32 This is in accordance with our results, showing increased risk for intellectual disability in both early-term and postterm birth.
The risk for perinatal mortality has been estimated to increase in term pregnancies with advancing GWs, from 0.7 per 1000 deliveries at week 37 to 5.8 per 1000 deliveries at week 43,9,27,33,34 which is in contrast with our data. The highest risk for perinatal mortality was related to early-term birth, as in certain studies.9,35 Several studies describe a U-shaped relationship of mortality with gestational age in term births.4,23
The overall risk for stillbirth is 1.6 to 5.3 per 1000 deliveries in developed countries.27,36 The risk for stillbirth is more accurately assessed by comparing stillbirth numbers with ongoing pregnancies.9,35 Calculated this way, the risk for stillbirth is lower in early-term birth than in full-term birth. In 1 study, risk for stillbirth and early neonatal death (≤7 days) was higher in countries with a large proportion of postterm deliveries (>4%),8 a fact we could not confirm. This may reflect the high quality of monitoring term and postterm pregnancies in Finland.
The study was divided into 5-year periods to enhance the evaluation of rare adverse outcomes and effects of recent changes in clinical management. As expected, perinatal mortality showed a tendency to decrease. Through the study period, the incidences of MAS and of low Apgar score at 1 minute increased, whereas the incidence of low umbilical artery pH did not vary. We found a decreasing incidence of CP in Finland during our study period, contrary to a recent finding of an unchanging overall worldwide prevalence of CP.17 The increased incidences of epilepsy, intellectual disability, and sensorineural defects may be explainable by improved diagnostics and advanced data-collecting systems.
The strength of our study was our large population-based cohort, which allows more consistent evaluation of rare events, such as perinatal death and CP. In addition, the Finnish population during the study period was quite homogeneous.
We encountered the limitations of all observational register-based studies. We had to restrict our factors to those available in the registers. Some conceivable confounding risk factors thus lacked any assessment. Data on the indication of delivery induction were unavailable in the MBR. The study population included high-risk pregnancies and children with congenital anomalies, either of which may have affected timing of delivery. Consequently, among early-term births, complicated pregnancies may be overrepresented. In such cases, delaying birth could lead to even worse neonatal outcomes. The MBR did not contain data on umbilical artery base excess, which is infrequently reported as an outcome measure of birth asphyxia, however.26 In the literature, 5-minute Apgar score is more common and has better prognostic value than 1-minute Apgar score.20 Unfortunately, the MBR contained only 1-minute Apgar score for the entire study period. Thus, the effect of low 5-minute Apgar score on adverse neurologic outcome is probably an underestimate. Analyses contained all diagnoses of palsy at the age of 4 years to include all children with CP. Among this age group other kinds of palsies are rare, but some children with such palsies may have been inaccurately diagnosed with CP. Furthermore, during the long study period, some obstetric practices changed, including pregnancy dating. However, when pregnancy dating is based on last menstrual period, the effect of gestational age on CP is usually underestimated.7
Gestational age at birth causes neonatal outcomes to vary. Risks for many complications are increased at both extremes of term and postterm birth. We observed increased risk for short- and long-term morbidity and perinatal mortality related to early-term birth. In postterm birth, the newborn’s risk for asphyxia was increased, although this had fewer long-term neurologic health impacts on the newborn; only the risk for intellectual disability was slightly increased. Furthermore, postterm birth led to no elevation in the incidence of perinatal mortality. Conceivably, birth at early-term may be related to risks concerning long-term neurologic health, whereas birth at postterm seems to involve fewer risks than previously assumed.
- Accepted March 24, 2016.
- Address correspondence to Laura Seikku, MD, Department of Obstetrics and Gynecology, University Central Hospital, Haartmaninkatu 2, 00029 HUS, Helsinki, Finland. E-mail:
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: The study was supported by Helsinki University Hospital Research grants (TYH2013340, TYH2014237), and grants by Finska Läkaresällskapet, The Foundation for Pediatric Research, Stiftelsen Dorothea Olivia, Karl Walter och Jarl Walter Perkléns Minne, and the Päivikki and Sakari Sohlberg Foundation.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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- Copyright © 2016 by the American Academy of Pediatrics