Asphyxia, Neurologic Morbidity,

and Perinatal Mortality in Early-

Term and Postterm Birth
Laura Seikku, MD,a Mika Gissler, MSocSci, PhD,b,c Sture Andersson, MD, PhD,d Petri Rahkonen, MD, PhD,d Vedran
Stefanovic, MD, PhD,a Minna Tikkanen, MD, PhD,a Jorma Paavonen, MD, PhD,a Leena Rahkonen, MD, PhDa

BACKGROUND AND OBJECTIVES: Neonatal outcomes vary by gestational age. We evaluated the abstract
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.

aDepartment of Obstetrics and Gynecology, and dChildren’s Hospital, University of Helsinki and Helsinki WHAT’S KNOWN ON THIS SUBJECT: Postterm birth
University Central Hospital, Helsinki, Finland; bInformation Department, National Institute for Health and is generally associated with higher risk for perinatal
Welfare, Helsinki, Finland; and cNordic School of Public Health, Gothenburg, Sweden morbidity and mortality, and long-term neurologic
Dr Seikku designed the study, carried out analyses, interpreted the data, and drafted the initial sequelae. The rate of postterm birth decreases, while the
manuscript; Dr Gissler designed the study, collected and analyzed the data, and reviewed and rate of early-term birth increases. Only recently, risks
revised the manuscript; Drs Andersson and P. Rahkonen conceptualized and designed the related to early-term birth have been recognized.
study, interpreted the data, and critically reviewed and revised the manuscript; Drs Stefanovic, WHAT THIS STUDY ADDS: Postterm birth causes a higher
Tikkanen, and Paavonen participated in designing the study and interpreting the data, and risk of birth asphyxia, but general long-term neurologic
reviewed and revised the manuscript; Dr L. Rahkonen conceptualized and designed the study,
morbidity is comparable with full-term birth. Among
coordinated and supervised data analyses, interpreted the data, and reviewed and revised
children born early-term, risks for low Apgar score and
the manuscript; and all authors approved the final manuscript as submitted and agree to be
long-term neurologic morbidity are increased.
accountable for all aspects of the work.
To cite: Seikku L, Gissler M, Andersson S, et al. Asphyxia, Neurologic Morbidity,
and Perinatal Mortality in Early-Term and Postterm Birth. Pediatrics.
2016;137(6):e20153334

PEDIATRICS Volume 137, number 6, Downloaded from http://pediatrics.aappublications.org/ by guest on May 23, 2018
June 2016:e20153334 ARTICLE
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.
METHODS
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
2 Downloaded from http://pediatrics.aappublications.org/ by guest on May 23, 2018
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
SEIKKU et al
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
Downloaded
PEDIATRICS Volume 137, number 6, June 2016
FIGURE 1
Diagnosis codes for selected primary neonatal outcomes and major neurologic impairments
according to ICD-9 (1989–1995) and ICD-10 (1996–2008).
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.
RESULTS
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).
Early Morbidity
The incidences of low Apgar score at
1 and 5 minutes, and low umbilical
artery pH ≤7.10 are shown in Fig 2.
from http://pediatrics.aappublications.org/ by guest on May 23, 2018
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
3
TABLE 1 Characteristics of the Study Population
Total Term Early-Term Postterm Versus
Early-Term Full-Term Postterm Versus Full-Term Full-Term

37+0–38+6 GW 39+0–41+6 GW ≥42+0 GW

n (%) n (%) n (%) n (%) Pa Pa
1 129 481 214 465 (19.0) 859 827 (76.1) 55 189 (4.9)
Study period, 5 y
1989–1993 304 929 (27.0) 56 201 (18.4) 233 560 (76.6) 15 168 (5.0)
1994–1998 285 729 (25.3) 55 138 (19.3) 217 471 (76.1) 13 120 (4.6)
1999–2003 263 857 (23.4) 51 573 (19.5) 199 990 (75.8) 12 294 (4.7)
2004–2008 274 966 (24.3) 51 553 (18.7) 208 806 (76.0) 14 607 (5.3)
Mother
Maternal age, mean (± SD) 29.7 (±5.3) 30.1 (±5.5) 29.5 (±5.3) 29.4 (±5.3) <.001 <.001
In vitro fertilization 15 759 (1.4) 5252 (2.5) 9962 (1.2) 545 (1.0) <.001 <.001
Smoking 168 671 (14.9) 33 432 (15.6) 126 201 (14.7) 9038 (16.4) <.001 <.001
Nulliparityb 453 889 (40.2) 83 331 (38.9) 341 561 (39.7) 28 997 (52.5) <.001 <.001
Mode of delivery
Spontaneous vaginal delivery 887 081 (78.5) 152 803 (71.2) 694 462 (80.8) 39 816 (72.1) <.001 <.001
Planned cesarean delivery 75 679 (6.7) 28 401 (13.2) 46 108 (5.4) 1170 (2.1) <.001 <.001
Emergency cesarean delivery 92 424 (8.2) 21 808 (10.2) 62 040 (7.2) 8576 (15.5) <.001 <.001
Vacuum extraction 67 365 (6.0) 9369 (4.4) 52 548 (6.1) 5448 (9.9) <.001 <.001
Forceps 1604 (0.1) 243 (0.1) 1273 (0.1) 88 (0.2) <.001 .498
Breech vaginal delivery 4437 (0.4) 1669 (0.8) 2714 (0.3) 54 (0.1) <.001 <.001
Induced delivery 166 794 (14.8) 33 780 (15.8) 108 175 (12.6) 24 839 (45.0) <.001 <.001
Newborn
Male 574 820 (50.9) 113 479 (52.9) 433 022 (50.4) 28 319 (51.3) <.001 <.001
Apgar at 1 min <4 9056 (0.8) 2031 (1.0) 6284 (0.7) 737 (1.3) <.001 <.001
Apgar at 5 min, nc 230 408 43 947 174 749 11 712
Apgar at 5 min <4 634 (0.3) 148 (0.3) 417 (0.2) 69 (0.59) <.001 <.001
Umbilical artery pH, nd 519 210 99 579 392 309 27 322
Umbilical artery pH <7.0 2613 (0.5) 513 (0.5) 1886 (0.5) 214 (0.8) .081 <.001
Umbilical artery pH 7.0–7.10 15 384 (3.0) 2202 (2.2) 11 902 (3.0) 1280 (4.7) <.001 <.001
Birth weight, ge
<2500 13 622 (1.2) 9858 (4.6) 3710 (0.4) 54 (0.1) <.001 .002
>4000 227 735 (20.2) 15 794 (7.4) 191 436 (22.3) 20 505 (37.2) <.001 <.001
Birth weight, mean (± SD) 3598 (±486) 3290 (±487) 3658 (±448) 3859 (±446) <.001 <.001
–2SD 21 343 (1.9) 4242 (2.0) 16 070 (1.9) 1031 (1.9) <.001 .998
+2SD 32 497 (2.9) 6270 (2.9) 24 691 (2.9) 1536 (2.8) .198 .233
Meconium aspiration 1891 (0.2) 143 (0.1) 1481 (0.2) 267 (0.5) <.001 <.001
a t-test, χ2 test, and test for relative proportions.
b Data missing on 1331 births.
c Data available on 230 408 births (years 2004–2008).
d Data available on 519 210 births.
e Data missing on 295 births.

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).
Long-term Morbidity
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).
Mortality
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

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TABLE 2 Risk Factor Analysis by Logistic Regression for Neurologic Morbidity: CP, Epilepsy, Intellectual Disability, and Sensorineural Defects
n= CP Adjusted OR (CI) Epilepsy Adjusted Intellectual Disability Sensorineural Defectsa
1 129 481 OR (CI) Adjusted OR (CI) Adjusted OR (CI)
Maternal risk factors
In vitro fertilization 15 759 0.82 (0.57–1.18) 1.09 (0.86–1.38) 0.79 (0.55–1.13) 1.11 (0.92–1.34)
Smoking 168 671 1.24 (1.11–1.39) 1.03 (0.95–1.12) 1.07 (0.96–1.19) 1.23 (1.16–1.31)
Nulliparityb 453 889 0.88 (0.80–0.97) 0.89 (0.83–0.95) 0.83 (0.75–0.90) 0.94 (0.90–0.99)
Maternal age <20 y 30 276 1.46 (1.15–1.84) 1.30 (1.10–1.55) 1.43 (1.13–1.79) 1.31 (1.15–1.50)
Maternal age >35 y 186 213 1.16 (1.03–1.29) 1.03 (0.96–1.12) 1.14 (1.02–1.26) 1.02 (0.96–1.09)
Planned cesarean delivery 75 679 1.43 (1.22–1.68) 1.43 (1.29–1.60) 1.21 (1.09–1.35) 1.21 (1.13–1.28)
Emergency cesarean 92 424 2.03 (1.80–2.29) 1.37 (1.25–1.52) 1.47 (1.30–1.68) 1.12 (1.03–1.22)
delivery
Vacuum extraction 67 365 1.08 (0.89–1.30) 1.17 (1.03–1.32) 1.37 (1.18–1.59) 1.18 (1.08–1.30)
Breech vaginal birth 4437 5.64 (2.30–13.81) 0.55 (0.08–3.92) 0.94 (0.13–6.78) N/Ac
Induced delivery 166 794 1.05 (0.94–1.18) 1.13 (1.04–1.22) 1.15 (0.97–1.36) 1.08 (0.98–1.20)
Newborn risk factors
Postterm birth, ≥42+0 GW 55 189 1.03 (0.84–1.26) 1.00 (0.87–1.15) 1.19 (1.00–1.43) 0.96 (0.86–1.07)
Early-term birth, 37+0–38+6 214 465 1.40 (1.27–1.55) 1.14 (1.06–1.23) 1.39 (1.27–1.53) 1.24 (1.17–1.31)
GW
Male 574 820 1.30 (1.19–1.42) 1.09 (1.03–1.16) 1.51 (1.39–1.64) 1.09 (1.04–1.14)
Apgar <4 at 1 min 9056 6.20 (5.13–7.49) 2.89 (2.39–3.51) 3.19 (1.39–1.64) 1.52 (1.24–1.86)
Apgar <4 at 5 min 634 2.20 (1.40–3.47) 2.30 (1.42–3.74) 2.82 (1.62–4.92) 1.93 (1.13–3.29)
Umbilical artery pH <7.00 2613 3.66 (2.70–4.96) 2.15 (1.53–3.01) 1.66 (1.02–2.68) 2.30 (1.70–3.12)
Umbilical artery pH 15 384 1.49 (1.13–1.96) 1.32 (1.06–1.64) 1.23 (0.91–1.66) 1.59 (1.35–1.87)
7.00–7.10
Birth weightd
–2SD 21 343 2.76 (2.30–3.31) 2.04 (1.75–2.38) 3.67 (3.11–4.32) 1.69 (1.48–1.92)
+2SD 32 497 1.02 (0.79–1.30) 0.79 (0.65–0.96) 0.76 (0.58–0.99) 0.90 (0.78–1.04)
Meconium aspiration 1891 1.54 (0.20–11.63) 1.54 (0.21–11.18) 5.19 (1.24–21.68) N/Ac
Logistic regression multivariate models were used, with results given as ORs and 95% CIs.
a Sensorineural defects included impairments of vision or hearing.
b Data missing on 1331 births.
c N/A, Not applicable.
d Data missing on 295 births.

statistically significant (P = .071)

(Fig 3).

DISCUSSION

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 FIGURE 2
morbidity, including CP, epilepsy, Incidences of low umbilical artery pH and low Apgar score at 1 and 5 minutes according to GWs.
and sensorineural defects, were not
more common, whereas intellectual many countries,15 but in Finland the rate of postterm birth increased
disability was. such routine inductions have during the 20-year study period.
been less frequent.8 Despite an Nevertheless, the incidences of
The rate of elective induction of increasing overall number of delivery perinatal mortality and long-term
delivery after 41 GW or even in the inductions,12 the rate of early-term morbidity in our study population
early-term period is increasing in birth did not vary substantially, and were comparable with those in

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PEDIATRICS Volume 137, number 6, June 2016 from http://pediatrics.aappublications.org/ by guest on May 23, 2018 5
TABLE 3 Neurologic Impairments at 4 Years of Age
Deliveries, n (%) CP, n (%) Epilepsy, n (%) Intellectual Disability, n (%) Sensorineural Defects,a n (%)
1 129 481 2298 (0.20) 4410 (0.39) 2337 (0.21) 7117 (0.63)
GWs
37+0–38+6 214 465 (19.0) 607 (0.28) 966 (0.45) 596 (0.28) 1638 (0.76)
39+0–41+6 859 827 (76.1) 1578 (0.18) 3222 (0.37) 1605 (0.19) 5135 (0.60)
≥42+0 55 189 (4.9) 113 (0.21) 222 (0.40) 136 (0.24) 344 (0.62)
Study period, 5 y
1989–1993 304 929 (27.0) 785 (0.26) 580 (0.19) 487 (0.16) 282 (0.09)
1994–1998 285 729 (25.3) 608 (0.21) 1234 (0.43) 525 (0.18) 1756 (0.62)
1999–2003 263 857 (23.4) 502 (0.19) 1287 (0.49) 630 (0.24) 2216 (0.84)
2004–2008 274 966 (24.3) 403 (0.15) 1309 (0.48) 695 (0.25) 2863 (1.04)
a Sensorineural defects included impairments of vision or hearing.

earlier studies.9,10,16,17 We did not TABLE 4 Risk for Perinatal Mortality in Early- and Postterm Birth as Compared With Full-Term Birth,
find the controversial association of Excluding Children With Major Congenital Anomalies
delivery induction with CP.18,19 Early-Term 37+0–38+6 GW Postterm ≥42+0 GW

In term deliveries, low Apgar score at OR (95% CI) OR (95% CI)

5 and 10 minutes frequently reflects Total perinatal mortalitya 2.40 (2.14–2.69) 0.91 (0.69–1.22)
perinatal asphyxia and acidosis, and Early neonatal death, ≤7 d 1.73 (1.25–2.40) 2.06 (1.31–3.25)
Stillbirthb 0.49 (0.43–0.55) 0.67 (0.46–0.98)
predicts neonatal morbidity and
a Including stillbirth and early neonatal death correlated with births on the specific GW.
mortality.20–22 Here, as in previous b Correlated with the number of ongoing pregnancies.
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
FIGURE 3
Perinatal mortality, defined as stillbirth and early neonatal death at ≤7 days of age, per 1000 term
and postterm newborns during the study period, excluding children with major congenital anomalies.
aberrations.27,28 The association of reported an association of epilepsy
CP with postterm birth has been with postterm birth.30 Conversely,
controversial in earlier studies with we found that postterm birth did not
early-term births often included lead to increased risk for epilepsy or
in their reference groups.7,29 A sensorineural defects, whereas early-
U-shaped pattern exists in risk for term birth did. Lower IQ occurs in
CP among term newborns, with early-term and postterm birth, with
the highest risk at 37 GW and at 42 the highest IQ at term.31,32 This is in
GW and beyond.7 Interestingly, we accordance with our results, showing
found the highest risk for CP at early- increased risk for intellectual
term, whereas postterm birth did disability in both early-term and
not show a higher risk. One study postterm birth.

6 Downloaded from http://pediatrics.aappublications.org/ by guest on May 23, 2018 SEIKKU et al

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
DOI: 10.1542/peds.2015-3334
Accepted for publication Mar 24, 2016
Address correspondence to Laura Seikku, MD, Department of Obstetrics and Gynecology, University Central Hospital, Haartmaninkatu 2, 00029 HUS, Helsinki,
Finland. E-mail: laura.seikku@hus.fi
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Downloaded
PEDIATRICS Volume 137, number 6, June 2016
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
from http://pediatrics.aappublications.org/ by guest on May 23, 2018
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
CONCLUSIONS
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.
ABBREVIATIONS
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
7
Copyright © 2016 by the American Academy of Pediatrics
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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9
Asphyxia, Neurologic Morbidity, and Perinatal Mortality in Early-Term and
Postterm Birth
Laura Seikku, Mika Gissler, Sture Andersson, Petri Rahkonen, Vedran Stefanovic,
Minna Tikkanen, Jorma Paavonen and Leena Rahkonen
Pediatrics originally published online May 27, 2016;

Updated Information & including high resolution figures, can be found at:
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015-3334
References This article cites 33 articles, 3 of which you can access for free at:
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015-3334.full#ref-list-1
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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
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Asphyxia, Neurologic Morbidity, and Perinatal Mortality in Early-Term and
Postterm Birth
Laura Seikku, Mika Gissler, Sture Andersson, Petri Rahkonen, Vedran Stefanovic,
Minna Tikkanen, Jorma Paavonen and Leena Rahkonen
Pediatrics originally published online May 27, 2016;

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/early/2016/05/25/peds.2015-3334

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright © 2016 by the American Academy of Pediatrics. All rights reserved. Print ISSN:
.

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