Objective
The purpose of this study was to determine whether placental pathologic condition supports the recent suggestion of subcategorizing preterm and term births into smaller gestational age subgroups with different perinatal mortality and morbidity rates.
Study Design
Twenty-seven clinical and 43 placental phenotypes were retrospectively compared in 4617 third-trimester births: 1332 preterm pregnancies (28-33 weeks’ gestation), 1066 late preterm pregnancies (34-36 weeks’ gestation), 940 near-term pregnancies (37-38 weeks’ gestation), and 1279 term pregnancies (≥39 weeks’ gestation).
Results
Acute inflammatory pattern of placental injury was seen mostly at both gestational sides of the third trimester; the clinical conditions linked to in utero hypoxia (preeclampsia, diabetes mellitus, fetal growth restriction) and their placental associations (atherosis, membrane chorionic microcysts, chorangiosis, intervillous thrombi) were associated statistically significantly with mid third trimester. Acute fetal distress (abnormal fetal heart tracing and clinical and histologic meconium) were increasing with gestational age and were statistically significantly most common in full-term pregnancies.
Conclusion
Differences in placental pathologic condition among the 4 subgroups of third-trimester pregnancy not only challenge the use of an arbitrary cutoff point of 37 weeks’ gestation that separates the preterm birth and term birth but also further support separation of late preterm births from preterm births and term births from near-term births. Based on placental pathologic condition, chronic uteroplacental malperfusion is the dominating etiopathogenetic factor in the mid third trimester (late preterm and near-term births), and acute fetal distress is the factor in full-term births. This obscures relative frequencies of perinatal death and management modalities in the third trimester.
Separation of third-trimester births into preterm (up to 36 completed gestational weeks) and term (≥37 gestational weeks) is time-honored. However, there is accumulating evidence that preterm and term births are not homogeneous groups with regard to maternal diagnoses and fetal morbidity and mortality profiles. It seems that prematurity by even a single week increases the risk of neonatal morbidity and death. Even at gestational week 37 (ie, the first week of term gestation), the morbidity rates are twice those at 38 weeks. The prematurity rates increase even without increasing prevalence of maternal risk factors such as preeclampsia, umbilical cord accidents, or chorioamnionitis. Other investigators found a 23% decrease of adverse outcomes with each week of advancing gestational age between 32 and 39 completed weeks; therefore, a more conservative approach was recommended for late preterm pregnancies. The term birth that previously was considered a homogeneous group to which risks that are associated with preterm and postterm births are compared forms a heterogeneous group, and the children who are born earlier in the term period (early term) and those who are born later must be considered as separate subgroups.
Placental examination is a well-recognized diary of pregnancy; its results are included as one of the major phenotypes in an assessment of preterm deliveries. Although the frequencies of various placental diagnoses vary with gestational age, the associations of various patterns of placental injury with the changing clinical phenotypes in the third-trimester gestational age intervals are largely unknown; assessment thereof is the goal of this retrospective analysis.
Methods
The project was approved by the institutional review board. Retrospectively, 27 clinical and 43 placental phenotypes were analyzed in all consecutive 4617 third-trimester births from which the placentas were examined from 1994-2012: 1332 preterm pregnancies (28-33 weeks’ gestation), 1066 late preterm pregnancies (34-36 weeks’ gestation), 940 near-term (early-term) pregnancies (37-38 weeks’ gestation), and 1279 term pregnancies (≥39 weeks’ gestation). The gestational age determination for this study was based on a combination of the first-trimester ultrasound scan (when available), last menstrual period, or obstetric estimate of gestational age. The data were extracted from the author’s clinical placental database that had been built from clinical charts and placental reports. There were no exclusion criteria; therefore, all types of perinatal death and morbidity, including stillbirths, were included. The postterm deliveries were included in the term group, because the precise definitions of the postterm pregnancy are somewhat obscure. Placentas had been submitted for examination at the discretion of obstetricians because of the high risk nature of pregnancy, fetal distress, poor condition of the neonate, operative delivery, or grossly abnormal placenta. Placental examination was performed according to generally accepted criteria; specifically, placental measurements and trimmed weights were recorded; at least 2 sections of placental membrane roll and umbilical cord and at least 2 paracentral full-thickness chorionic disc sections routinely were taken as a part of placental examination if no gross lesions were identified. All gross lesions that were seen were additionally sampled. The samples were fixed in buffered formalin, followed by routine paraffin embedding, cutting, and staining with hematoxylin and eosin. Definitions of clinical conditions and placental diagnoses were either standard or the same as reported by the author separately. The statistical analysis compared the clinical and placental phenotypes of the adjacent third-trimester intervals with the use of the Yates χ 2 test followed by the Holm-Bonferroni correction for multiple comparisons.
Results
The analyzed clinical complications and outcomes and placental phenotypes were seen in all 4 gestational age intervals, which indicated the continuity and overlapping of pathophysiologic condition in the third trimester of pregnancy ( Table ). However, the frequencies of particular clinical and placental phenotypes in the placentas from high-risk patients in 4 gestational age intervals varied.
| Variable | 28-33 wks, n (%) | Yates χ 2 | P value | 34-36 wks, n (%) | Yates χ 2 | P value | 37-38 wks, n (%) | Yates χ 2 | P value | ≥39 wks, n (%) |
|---|---|---|---|---|---|---|---|---|---|---|
| Cases | 1332 | 1066 | 940 | 1279 | ||||||
| Clinical variables | ||||||||||
| Preeclampsia | 153 (11.5) | 120 (11.3) | 71 (7.5) | 8.5 | .003 a | 58 (4.5) | ||||
| Mild | 35 (2.6) | 9.8 | .001 a | 55 (5.2) | 41 (4.4) | 43 (3.4) | ||||
| Maternal diabetes mellitus | 69 (5.2) | 6.8 | .009 | 84 (7.9) | 86 (9.1) | 28.9 | 8e-8 a | 46 (3.6) | ||
| Premature rupture of membranes | 296 (22.2) | 43.5 | <1e-8 a | 126 (11.8) | 28.6 | 9e-8 a | 47 (5.0) | 79 (6.2) | ||
| Meconium (clinical) | 30 (2.5) | 34 (3.2) | 10.1 | .001 a | 59 (6.3) | 65.2 | <1e-8 a | 231 (18.1) | ||
| Thin | 23 (1.7) | 26 (2.4) | 4.6 | .003 | 40 (4.2) | 21.6 | .000003 a | 122 (9.5) | ||
| Thick | 7 (0.5) | 8 (0.7) | 5.2 | 0.023 | 9 (2.0) | 40.9 | <1e-8 a | 109 (8.5) | ||
| Abnormal fetal heart rate tracing b | 204 (15.3) | 150 (14.1) | 155 (16.5) | 26.5 | 2.6e-7 a | 329 (25.7) | ||||
| Induction of labor | 55 (4.1) | 19.3 | .00001 a | 91 (8.5) | 101 (10.7) | 124 (9.7) | ||||
| Perinatal mortality | 175 (13.1) | 32.8 | 1e-8 a | 64 (6.0) | 57 (6.1) | 83 (6.5) | ||||
| Neonatal | 53 (4.0) | 14.5 | .0001 a | 14 (1.3) | 11 (1.2) | 17 (1.3) | ||||
| Macerated stillbirth | 91 (6.8) | 12.6 | .0004 a | 37 (3.5) | 32 (3.4) | 44 (3.4) | ||||
| Multiple pregnancy | 208 (15.6) | 177 (16.6) | 24.5 | 7.5e-7 a | 85 (9.0) | 67.6 | <1e-8 a | 19 (1.5) | ||
| Fetal growth restriction c | 122 (9.2) | 13.7 | .002 a | 150 (14.1) | 153 (16.3) | 72.7 | <1e-8 a | 67 (5.2) | ||
| Congenital malformations | 84 (6.3) | 59 (5.5) | 69 (7.3) | 11.9 | .0006 a | 50 (3.9) | ||||
| Abnormal third stage of labor (prolonged, hemorrhage) | 344 (2.5) | 204.0 | <1e-8 a | 44 (4.1) | 44 (4.7) | 58 (4.5) | ||||
| Placental variables | ||||||||||
| Acute chorioamnionitis | 459 (34.5) | 50.4 | <1e-8 a | 226 (21.2) | 5.5 | 0.018 | 242 (25.7) | 80.0 | <1e-8 a | 567 (44.3) |
| Maternal inflammatory response | 310 (23.3) | 16.8 | .00004 a | 175 (16.4) | 5.9 | 0.015 | 195 (20.7) | 41.8 | <1e-8 a | 426 (33.3) |
| Fetal inflammatory response | 149 (11.2) | 55.5 | <1e-8 a | 51 (4.8) | 47 (5.0) | 24.6 | 7.1e-7 a | 141 (11.0) | ||
| Fetal hypoxic lesions | ||||||||||
| Meconium (histological) | 208 (15.6) | 38.8 | <1e-8 a | 277 (26.0) | 54.8 | <1e-8 a | 392 (41.7) | 80.1 | <1e-8 a | 780 (61.0) |
| Shallow | 171 (12.8) | 37.0 | <1e-8 a | 238 (22.3) | 33.0 | 1e-8 a | 319 (33.9) | 26.9 | 2.1e-7 a | 575 (45.0) |
| Deep | 37 (2.8) | 39 (3.7) | 15.27 | .00009 a | 319 (33.9) | 205 (16.0) | ||||
| Maternal hypoxic lesions | ||||||||||
| Atherosis of spiral arterioles | 93 (7.0) | 11.9 | .0005 a | 39 (3.7) | 25 (2.7) | 18 (1.4) | ||||
| Uterine pattern of chronic hypoxic injury | 100 (7.5) | 80 (7.5) | 11.7 | .0006 a | 36 (3.8) | 31 (2.4) | ||||
| Membrane microscopic chorionic pseudocysts d | 93 (7.0) | 4.3 | .038 | 100 (9.4) | 86 (9.1) | 6.9 | .008 a | 7.8 (6.1) | ||
| Chorangiosis | 157 (11.8) | 12.3 | .0004 a | 180 (16.9) | 159 (16.9) | 201 (15.7) | ||||
| Intervillous thrombus | 89 (6.7) | 8.9 | .003 a | 108 (10.1) | 114 (12.1) | 154 (12.0) |
a P values that remained statistically significant after the Holm-Bonferroni correction. The “e” signifies conversion of the scientific to the decimal notation; eg, “8e-8” = 0.00000008
b Abnormal nonstress test and/or abnormal contraction stress test and/or abnormal intrapartum cardiotocography (prolonged bradycardia and/or prolonged tachycardia and/or decrease of fetal heart rate variability and/or late decelerations)
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