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American Journal of Obstetrics and Gynecology (2005) 192, 185e90

www.ajog.org

Neonatal complications of term pregnancy: Rates by


gestational age increase in a continuous,
not threshold, fashion
Aaron B. Caughey, MD, MPP, MPHa,b A. Eugene Washington, MD, MSc,a
Russell K. Laros, Jr, MDa

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, Calif, a
and Division of Health Services and Policy Analysis, University of California, Berkeley, Calif b

Received for publication April 25, 2004; revised June 11, 2004; accepted June 21, 2004

KEY WORDS Objective: The purpose of this study was to determine whether, when, and how rates of short-
Perinatal morbidity term neonatal complications increase beyond 37 weeks of gestation.
Postterm pregnancy Study design: A retrospective cohort study was conducted of all low-risk, term, cephalic, and
Postdates pregnancy singleton births that were delivered at the University of California, San Francisco, between 1976
and 2001. Primary outcomes included neonatal umbilical artery pH, umbilical artery base excess,
the presence of meconium, macrosomia, 5-minute Apgar scores, and admission to the intensive
care nursery. Multivariate analyses were performed that controlled for maternal ethnicity, weight,
age, socioeconomic status, and obstetric history.
Results: Among the 32,679 women who were delivered at R37 completed weeks of gestation, the
rates of umbilical artery pH !7.0, umbilical artery base excess less than 12 increased beyond 40
weeks of gestation, and the presence of meconium increased beyond 39 weeks of gestation (chi-
squared test; P ! .001). These outcomes continued to increase in each subsequent week, and these
findings persisted when they were controlled for potential confounders in multivariate models.
Conclusion: We found that the rates of immediate neonatal morbidity increase with increasing
gestational age. Accurate determination of these rates is important in the determination of
gestational age at which the risk of continuing the pregnancy outweighs the risk of induction of
labor.
Ó 2005 Elsevier Inc. All rights reserved.

Clifford et al1 noted that, although pregnancies which deaths. Thus, since the advent of antenatal fetal
persisted beyond 43 weeks of gestation occurred !5% surveillance, one intent has been the prevention of fetal
of the time, they accounted for 30% of the perinatal death among postterm pregnancies. In the 1970s and
1980s, this was defined commonly as patients beyond 42
completed weeks of gestation, or 294 days,2 which
Supported in part by the National Institute of Child Health and
complicates O10% of pregnancies.3 In addition to an
Human Development, grant # HD01262 (A.B.C.). increased perinatal mortality rate,4-8 numerous studies
Reprints not available from the authors. have associated postterm pregnancies with increased

0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.ajog.2004.06.068
186 Caughey, Washington, and Laros

rates of neonatal morbidity, which includes meconium rather than simple dichotomous comparisons, we sought
and meconium aspiration syndrome,4,9,10 oligohydram- to explore neonatal complications of pregnancy O37
nios,11 macrosomia,4,10,12 and fetal birth injury.13 How- weeks of gestation in an otherwise low-risk cohort of
ever, most of these studies that examine gestational age patients. Specifically, we were interested in determining
do so by establishing thresholds such as 41 or 42 weeks at what gestational age the rates of neonatal complica-
of gestation and comparing rates of complications tions increase over the previous week of gestation.
beyond this threshold to those in patients who are Further, we were interested in whether these complica-
delivered below the threshold. tions continued to increase beyond the initial rise and in
This type of comparison, which may have been used what fashion.
in earlier studies to increase statistical power, can lead to
several false conclusions. First, if the rate of complica-
tions just before the threshold is similar to that just Methods
beyond the threshold, but the rate goes down much
earlier, on average it may seem that the rate increases We designed a retrospective cohort study of all single-
beyond the threshold. Conversely, if the complications ton, cephalic, low-risk neonates who were delivered at
beyond the threshold are at first no different but then O37 weeks of gestation from January 1, 1976, to
increase dramatically, it might seem that, on average, December 1, 2001, at the Moffitt-Long Hospital associ-
patients above that threshold are at higher risk for the ated with the University of California, San Francisco.
complications. Clinically, patients and their physicians Exclusion criteria included delivery !37 weeks of
wish to know what the risk is of continuing a pregnancy gestation and pregnancies that were complicated by
beyond any given point over the next time interval and, diabetes mellitus, preeclampsia, chronic hypertension,
in particular, whether the risk of a given complication collagen vascular disease, fetal anomalies, nonecephalic
increases compared with the previous time interval. presentation, placenta previa, previous cesarean deliv-
Thus, the types of analyses that analyze risks by ery, and multiple gestation. At our institution, umbilical
thresholds are of much less use clinically than an artery and vein blood gases are obtained on every
analysis that considers the rates of complications by neonate. Information on the following outcomes were
week of gestation. Studies that have examined the risk of collected: umbilical artery pH, umbilical artery base
fetal death by the week of gestational age demonstrate excess, presence of meconium, macrosomia (O4500 g),
that rates increase in a steadily rising fashion, as admission to the ICN, 5-minute Apgar scores, birth
opposed to a sudden jump beyond a given thresh- trauma (including skull fracture and brachial plexus
old.14,15 If this complication of pregnancy increases, injuries), neonatal seizures, intracranial hemorrhage,
not as a discrete risk beyond some particular gestational neonatal sepsis, meconium aspiration syndrome, and
age, but instead continuously with increasing gestational respiratory distress syndrome. The following variables
age, other neonatal complications that are associated were examined as confounders: maternal age, ethnicity,
with postterm pregnancies may do the same. education, length of labor, mode of delivery, year of
Although the rates of low Apgar scores and intensive delivery, parity, anesthesia, birth weight, and labor
care nursery (ICN) admissions have been examined and management (induction of labor, augmentation of labor
shown to increase by week of gestation,10 other short- through artificial rupture of membranes, and augmen-
term neonatal measures of long-term morbidity have tation of labor with oxytocin). This study was approved
not. In one study of umbilical artery pH !7.0 and 5- by the investigational review board at the University of
minute Apgar scores !4, no difference between 40, 41, California, San Francisco.
and 42 weeks of gestation was shown, although the The data were then compiled and analyzed with
authors did find an increase in neonatal sepsis.16 STATA software (version 7; Stata Corporation, College
Although 5-minute Apgar scores both !4 or 7 have Station, Tex). Because the primary predictor of interest
been associated with poor long-term outcomes,17 other was gestational age by week, the dependent variables of
authors suggest that newborn umbilical artery acid-base interest were compared in a bivariate fashion with
status is a more predictive short-term measure of long- gestational age from R37 weeks. Because the outcomes
term neonatal outcome.18 Umbilical artery base excess of interest were neonatal rather than fetal, the de-
less than 12 has been cited as a particularly useful nominator used to calculate rates was all pregnancies
threshold.19 A recent study suggested that a pH !7.0 that were delivered during the particular week of
had relatively good sensitivity (74%) for the identifica- gestation. Because the rates of many of the neonatal
tion of neonates who would undergo early neonatal complications were low, a summary variable called
seizures as the result of hypoxic ischemic encephalopa- severe complications was created that included birth
thy.20 trauma (including skull fracture and brachial plexus
Given this background, and a particular intent to injuries), neonatal seizures, intracranial hemorrhage,
examine neonatal complications by week of gestation neonatal sepsis, meconium aspiration syndrome, and
Caughey, Washington, and Laros 187

respiratory distress syndrome. Comparisons of propor-


Table I Demographics and descriptive obstetric outcomes
tions were made with the use of the c2 test; means were
compared with the use of the Student t test. For those Percentage of low-risk
Variable patients
variables of interest and those variables that exhibited
an increasing bivariate trend with increasing gestational Maternal age R35 y 14.8
age, a multivariate logistic regression was performed College graduate 51.5
that included potential confounders and used dummy Medicaid insurance 39.4
Ethnicity
variables for each week of gestation in the model as
Black 11.8
independent variables. Cross product terms to examine Asian 26.3
interaction between predictor variables were created. Hispanic 9.4
Their contribution to the model was tested with the White 39.0
maximum likelihood ratio test and were kept only in the Other (Native American, 13.5
model if they were statistically significant. Statistical unknown)
significance was defined as a probability value of !.05. Nulliparous 52.1
Birth weight R4000 g 12.6
Cesarean delivery 17.6
Operative vaginal delivery 15.0
Results
During the study period, there were 36,947 women who
were delivered at O37 completed weeks of gestation. We
Table II Abnormal neonatal acid-base status or 5-minute
excluded 4268 patients (11.6%) who fell into 1 of the
Apgar scores
high-risk groups (preeclampsia, diabetes mellitus, colla-
gen vascular disease, previous cesarean delivery, pla- Gestational N UA pH UA base excess 5-min Apgar
centa previa), were non-cephalic, or had a multiple age (wk) !7.0 (%) less than 12 (%) !7 (%)
gestation. This left 32,679 low-risk patients for analysis. 37 2053 0.85 0.92 4.22
These patients were ethnically diverse and relatively 38 4489 0.75 0.72 2.15*
well-educated, as indicated by the 51.5% who had 39 7626 0.78 1.02 1.83
completed 4 years of college (Table I). When short-term 40 9808 0.50 0.89 1.78
41 5717 1.09* 1.72y 2.68*
neonatal outcomes were examined by week of gestation,
42 2312 1.43* 2.03z 3.82*
there was a statistically significant increase in the rates 43 674 1.33 2.68z 3.35
of umbilical artery pH !7.0 and base excess less than
Statistical significance as compared with the rate of complication in
12 (Table II) in patients who were delivered at 41
the previous week of gestation.
weeks of gestation, compared with those patients who * P ! .01, c2 test.
were delivered at 40 weeks of gestation. This held true y
P ! .001, c2 test.
z
for 5-minute Apgar scores !7 and ICN admissions P ! .05, c2 test.
(Table III). When rates of meconium-stained fluid and
macrosomia were examined, these rates began to in-
crease to O38 weeks of gestation and continued in- beyond 41 weeks of gestation, the rates of umbilical
creasing through 42 weeks, when compared with the artery pH !7.0, and base excess less than 12 were
rates in the previous week (Table III). When we increased, as were the rate of 5-minute Apgar scores !7.
examined the rates of most of the more severe neonatal These rates continued to increase beyond 42 weeks of
complications, as we suspected, the actual numbers were gestation. After being controlled for confounders, both
too low to have adequate power to be examined by week the rates of meconium aspiration syndrome and the
of gestation. However, when we examined the summary overall rates of severe neonatal complications were
variable, severe complications, we did find an increasing increased to O40 weeks of gestation.
trend by week of gestation at O40 weeks of gestation To further examine how increasing a week of
(Table III). gestation affected neonatal acid-base status, we first
We next examined gestational age as a predictor for looked at the mean umbilical artery pH and base excess
these short-term neonatal outcomes using multivariate values by gestational age. We found that these values
logistic regression to control for maternal age, ethnicity, both tended to decrease with increasing gestational age
education, parity, mode of delivery, birth weight, length (Figures 1 and 2). Multivariate linear regression was
of labor, and induction. Beyond 40 weeks, gestational then used to examine umbilical artery pH and base
age was found to predict an increased risk for meco- excess. Considering just those deliveries 39 weeks and
nium-stained fluid and macrosomia (Table IV), when beyond, by increasing one week of gestation, the mean
compared with pregnancies that were delivered at 39 pH is lowered by 1% or approximately .06 (P ! .001)
weeks of gestation. Similar to the bivariate comparisons, and the base excess is lowered by 31% (P ! .001). These
188 Caughey, Washington, and Laros

Table III Neonatal complication rates by week of gestation


Gestational age (wk) N Meconium (%) Macrosomia (%) ICN admissions (%) Severe complications (%)*
37 2053 11.0 0.58 8.5 3.56
38 4489 13.8y 0.88y 4.5z 1.95x
39 7626 18.3z 1.15y 3.1y 1.84
40 9808 25.8z 2.22x 2.6 2.31y
41 5717 31.9z 3.58z 3.4x 3.14x
42 2312 35.4y 5.89z 4.7x 3.82x
43 674 37.2 8.57y 4.9 4.55y
Statistical significance as compared with the rate of complication in the previous week of gestation.
* Included birth trauma (including skull fracture and brachial plexus injuries), neonatal seizures, intracranial hemorrhage, neonatal sepsis, meconium
aspiration syndrome, and respiratory distress syndrome.
y
P ! .05, c2 test.
x
P ! .01, c2 test.
z
P ! .001, c2 test.

Table IV Association of gestational age with perinatal complications in multivariate model*


Gestational age odds ratio (95% CI)
Outcome 40 weeks 41 weeks 42 weeks
5-minute Apgar 0.97 (0.77, 1.22) 1.36 (1.07, 1.74) 1.71 (1.27, 2.30)
score, !7
UA pH !7.0 0.75 (0.42, 1.33) 1.65 (1.01, 2.77) 2.31 (1.25, 4.27)
UA BE ! 12 0.89 (0.65, 1.21) 1.59 (1.17, 2.16) 2.14 (1.49, 3.08)
Meconium 1.56 (1.44, 1.69) 2.04 (1.87, 2.22) 2.39 (2.13, 2.68)
Macrosomia 2.32 (1.71, 3.13) 4.26 (3.16, 7.14) 5.62 (4.02, 7.85)
ICN admissions 0.91 (0.74, 1.11) 0.99 (0.79, 1.24) 1.46 (1.13, 1.91)
Meconium aspiration 2.18 (1.26, 3.78) 3.35 (1.93, 5.84) 4.09 (2.07, 8.08)
Severe complications 1.47 (1.09, 1.98) 2.04 (1.50, 2.78) 2.37 (1.63, 3.49)
Severe complications included birth trauma (including skull fracture and brachial plexus injuries), neonatal seizures, intracranial hemorrhage, neonatal
sepsis, meconium aspiration syndrome, and respiratory distress syndrome.
* Each outcome was examined in a separate multivariate analysis and compared with pregnancies that were delivered at 39 weeks of gestation and
was controlled for maternal demographics, length of labor, induction, mode of delivery, and birth weight (except macrosomia). The odds ratios (95% CIs)
that do not cross unity are bolded.

findings were consistent with the trends in the mean pH deaths and, in particular, are associated with meconium
and mean base excess values, which both decreased at aspiration syndrome21 and birth injury, respectively.22
O39 weeks of gestation (P ! .01 for both, Student Further, we found that that the rate of meconium
t test). Cross-product terms were not found to be aspiration syndrome did increase beyond 40 weeks of
significant in any of the multivariate models and were gestation as did the overall rate of severe neonatal
not used in the final models. complications.
Our rates and trends by gestational age of umbilical
artery pH !7.0 differ from those reported by the only
Comment other study in the literature that examined neonatal
umbilical artery pH by the week of gestation.16 How-
When we examined neonatal acid-base status, we found ever, although the other analysis was limited to exam-
that both the umbilical artery pH and base excess ining pH !7.0, we also examined base excess less than
decreased in a continuous fashion after 39 weeks of 12, mean pH, and mean base excess and found the
gestation. Further, when we examined the rates of term same trends in all 4 measures. Interestingly, although we
neonates who had umbilical artery pH !7.0 and base found that the mean pH and base excess decrease at
excess less than 12, we found that the rates increased O39 weeks of gestation, this did not lead to meaningful
beyond 41 weeks of gestation. Other complications increases in the rates of neonatal acidemia until 41
(such as rates of meconium and macrosomia) increased weeks of gestation was reached.
in pregnancies beyond 38 weeks of gestation. These When managing patients who have progressed be-
findings are markers for other neonatal morbidity and yond their estimated date of confinement, our goal as
Caughey, Washington, and Laros 189

Figure 1 Mean umbilical artery pH (uapH) by week of


gestation. All differences between weeks are statistically
significant, except 37 to 38 weeks of gestation. Figure 2 Mean umbilical artery base excess (uaBE) by week
of gestation. All differences between weeks are statistically
significant, except 37 to 38 and 38 to 39 weeks of gestation.
clinicians is to minimize both maternal and neonatal
complications. Maternal complications of pregnancy
that include cesarean delivery,10,16 operative vaginal threshold to be at 42 weeks of gestation.3 However, on
delivery,10,16 3rd- and 4th-degree perineal lacerations,10 the basis of these data and existing literature, we would
and preeclampsia23 have all been shown to increase with suggest that this threshold should be reconsidered.
increasing gestational age. Further, the rate of cesarean Our study is not without limitations. A retrospective
delivery has been shown to decrease when patients study can be compromised by having multiple con-
undergo routine induction at 41 weeks of gestation, as founding variables. In our analysis, we controlled for
compared with expectant management with antenatal these confounders in two ways. First, we limited our
testing.24 In our analysis, we found that a number of analysis to low-risk patients. Second, we used multivar-
short-term neonatal complications also increased with iate models to control for maternal demographics,
increasing gestational age. Certainly, all of our measures obstetric history, and labor management and outcomes.
increased beyond 41 weeks, as compared with 40 weeks Although we did not have information on all confound-
of gestation. ers, we attempted to control for those that we consid-
If antenatal testing is begun at an earlier gestational ered important to these outcomes. Further, we did not
age, it is reasonable to assume that more patients with have all the information on our patients’ socioeconomic
a need for delivery will be identified. The suspicion has status, in particular income, and used education as
been that the induction of labor increases the rate of a proxy. Another possible limitation pertains to the
cesarean delivery,25 although most studies that support generalizability of our study population to that of all
this finding have not been randomized, controlled trials. pregnant women. The patients in our study were treated
Conversely, when Hannah et al24 randomly assigned at an academic center in California where the use of
patients to the induction of labor at 41 weeks of elective induction of labor rarely is performed. Other
gestation, they found a decrease in the rate of cesarean than this, our patient population represented a wide
deliveries. In a recent meta-analysis of the 16 random- spectrum of ethnicities, age, and educational status.
ized, controlled trials in the literature, the overall effect Furthermore, when we controlled for the various
that was found was also a decrease in the rate of maternal characteristics, our findings were robust.
cesarean delivery.26 Further, the efficacy and risk profile The determination at what gestational age pregnancy
of the existing and new methods for labor induction complications are increased is important in the
have continued to improve over time. Thus, we will need determination of both when pregnancies should be
to reassess the risks and the benefits from expectant screened for complications with antenatal fetal testing
management versus labor induction in these patients and when a delivery plan should be initiated. Our
with only the most current data. If labor induction findings suggest that some neonatal complications in-
methods improve and the risks of increasing gestational crease at beyond 39 weeks of gestation. Whether
age begin earlier than previously suspected, there may be beginning antenatal fetal testing earlier to identify some
an indication to intervene at an earlier gestational age. of these potential complications will lead to better
Given our data, it may be found that the balance of risks outcomes must be examined in large prospective trials.
and benefits for intervention in low-risk pregnancies Further, the effect of false-positive rates in such screen-
should be earlier than the current management. The ing protocols should be considered. At the very least,
most recent recommendations by the American College our findings suggest that the optimal gestational age to
of Obstetricians and Gynecologists have defined that initiate delivery requires further investigation.
190 Caughey, Washington, and Laros

References 15. Yudkin PL, Wood L, Redman CW. Risk of unexplained stillbirth
at different gestational ages. Lancet 1987;1:1192-4.
1. Clifford SH, Reid DE, Worcester J. Postmaturity. Am J Dis Child 16. Alexander JM, McIntire DD, Leveno KJ. Forty weeks and
1951;82:232-5. beyond: pregnancy outcomes by week of gestation. Obstet Gynecol
2. Hauth J, Goodman MT, Gilstrap LC 3rd, Gilstrap JE. Post-term 2000;96:291-4.
pregnancy. Obstet Gynecol 1980;56:467-70. 17. Thorngren-Jerneck K, Herbst A. Low 5-minute Apgar score:
3. American College of Obstetricians and Gynecologists. Manage- a population-based register study of 1 million term births. Obstet
ment of post-term pregnancy. Washington, DC: The College; 1997. Gynecol 2001;98:65-70.
Practice Patterns No.: 6. 18. Low JA, Lindsay BG, Derrick EJ. Threshold of metabolic acidosis
4. Bochner CJ, Williams III J, Castro L, Medearis A, Hobel CJ, associated with newborn complications. Am J Obstet Gynecol
Wade M. The efficacy of starting postterm antenatal testing at 41 1997;177:1391-4.
weeks as compared with 42 weeks of gestational age. Am J Obstet 19. Ross MG, Gala R. Use of umbilical artery base excess: algorithm
Gynecol 1988;159:550-4. for the timing of hypoxic injury. Am J Obstet Gynecol 2002;187:
5. Rand L, Robinson J, Economy KE, Norwitz ER. Post-term 1-9.
induction of labor revisited. Obstet Gynecol 2000;96:779-83. 20. Williams KP, Singh A. The correlation of seizures in newborn
6. Divon MY, Haglund B, Nisell H, Otterblad PO, Westgren M. infants with significant acidosis at birth with umbilical artery cord
Fetal and neonatal mortality in the postterm pregnancy: the gas values. Obstet Gynecol 2002;100:557-60.
impact of gestational age and fetal growth restriction. Am J Obstet 21. Nathan L, Leveno KJ, Carmody TJ, Kelly MA, Sherman ML.
Gynecol 1998;178:726-31. Meconium: a 1990s perspective on an old obstetric hazard. Obstet
7. Feldman GB. Prospective risk of stillbirth. Obstet Gynecol Gynecol 1994;83:329-32.
1992;79:547-53. 22. Gregory KD, Henry OA, Ramicone E, Chan LS, Platt LD.
8. Hilder L, Costeloe K, Thilaganathan B. Prolonged pregnancy: Maternal and infant complications in high and normal
evaluating gestation-specific risks of fetal and infant mortality. weight infants by method of delivery. Obstet Gynecol 1998;
BJOG 1998;105:169-73. 92:507-13.
9. Usher RH, Boyd ME, McLean FH, Kramer MS. Assessment of 23. Caughey AB, Stotland NE, Escobar G. What is the best measure
fetal risk in postdate pregnancies. Am J Obstet Gynecol of maternal complications of term pregnancy: Ongoing pregnan-
1988;158:259-64. cies or pregnancies delivered? Am J Obstet Gynecol 2003;
10. Caughey AB, Musci TJ. Complications of term pregnancies 189:1047-52.
beyond 37 weeks of gestation. Obstet Gynecol 2004;103:57-62. 24. Hannah ME, Hannah WJ, Hellmann J, Hewson S, Milner R,
11. Moore TR, Cayle JE. The amniotic fluid index in normal human Willan A. Induction of labor as compared with serial antenatal
pregnancy. Am J Obstet Gynecol 1990;162:1168-73. monitoring in post-term pregnancy. N Engl J Med 1992;326:
12. McLean FH, Boyd ME, Usher RH. Postterm infants: Too big or 1587-92.
too small? Am J Obstet Gynecol 1991;164:619-24. 25. Heffner LJ, Elkin E, Fretts RC. Impact of labor induction,
13. Campbell MK, Ostbye T, Irgens LM. Post-term birth: risk factors gestational age, and maternal age on cesarean delivery rates.
and outcomes in a 10-year cohort of Norwegian births. Obstet Obstet Gynecol 2003;102:287-93.
Gynecol 1997;89:543-8. 26. Sanchez-Ramos L, Olivier F, Delke I, Kaunitz AM. Labor
14. Raymond EG, Cnattingius S, Kiely JL. Effects of maternal age, induction versus expectant management for postterm pregnancies:
parity, and smoking on the risk of stillbirth. BJOG 1994;101: a systematic review with meta-analysis. Obstet Gynecol 2003;
301-6. 101:1312-8.