Objective
To investigate the antenatal suspicion of placental disease and the coexistence of maternal and fetal placental ischemic disease.
Study Design
A prospective cohort study on normally formed singleton infants from 2000 to 2008 inclusive with placental ischemic disease.
Results
Uteroplacental ischemia or fetoplacental thrombotic vasculopathy was identified in 511 of 74,857 births (7/1000 births). Four hundred fifty-nine cases met the inclusion criteria. Maternal and fetal placental vascular disease coexisted in 9.2% (n = 42) of cases. Placental ischemic disease was suspected antenatally in 70% (324/459). Maternal placental disease occurred in 40% (184/459) and 30% (140/459) had fetal pathology. The perinatal mortality rate was 12.7/1000. Antenatal suspicion of placental disease led to increased obstetric intervention and delivery of small-for-gestational age infants.
Conclusion
Maternal and fetoplacental vascular disease coexisted in 9.2%. Placental disease was suspected antenatally in 70% of cases and was associated with increased rates of obstetric intervention.
The placenta has 2 circulations and either or both may show vascular disease. Placental vascular disease may be maternal as manifest by uteroplacental ischemia (UPI), or fetal with fetoplacental thrombotic vasculopathy (FTV). Either may be associated with increased perinatal morbidity and mortality.
Placental disease is usually a diagnosis that is achieved after delivery of the infant. However, there is little in the literature about the accuracy of the antenatal clinical suspicion of placental disease. We hypothesized that placental ischemic disease could be suspected antenatally secondary to maternal or fetal clinical complications, and that the obstetric outcome would differ when compared with pregnancies where placental disease is not suspected antenatally.
In addition few authors have examined the coexistence of maternal and fetal placental disease and its associated clinical outcome. The secondary hypothesis was that maternal and fetal placental ischemic disease may coexist. Such coexistence could suggest a common cause such as inherited thrombophilia. We aimed to record incidence of coexisting maternal and fetal placental disease and to compare obstetric outcome in these cases with cases with maternal placental ischemic disease only.
The purpose of this study therefore was to examine the obstetric outcomes of cases with antenatal suspicion of placental ischemic disease and to record the incidence of coexisting maternal and fetal placental disease.
Materials and Methods
A prospective cohort study was conducted on normally formed infants from Jan. 1, 2000, to Dec. 31, 2008, inclusive. All cases had a routine single ultrasound at 18-22 weeks to confirm gestation and review anatomy. All cases with anomaly, multiple pregnancies and incomplete data were excluded from the study.
All cases were identified following a triage system in our laboratory where all cases with antenatal maternal or fetal disease, abnormal gross placental pathology, or adverse obstetric outcome undergo placental analysis. This highlights one-third of all placentae for examination. These cases form the basis of the denominator. Cases are further triaged for gross examination only or histologic examination.
This study examines a subset in which maternal or fetal placental ischemic disease was identified on histologic examination. All cases were prospectively coded in a laboratory database by one of the authors (E.M.).
At delivery, the umbilical cord was clamped (ie, both on the infant and placental side when cut). The placenta was measured in its longest dimension and in the dimension perpendicular to that. The umbilical cord length was measured from cord insertion to the cord clamp. In our hospital a segment of the umbilical cord is not removed for fetal cord blood gas assessment.
Placentas were weighed fresh. The placenta was weighed trimmed of cord and membranes and the weight was recorded to the nearest 5 g. Cord length diameter and insertion were recorded. Circumvallate placentation was considered to constitute placental disease, whereas circummargination was not.
Two portions from the central two thirds of the placenta and samples from all central gross lesions were placed in 10% buffered formalin and standard hematoxylin and eosin (H&E) sections prepared. One section of cord and membranes and 5 sections of placental parenchyma were reviewed. This included at least 2 sections of grossly normal placenta.
Maternal placental ischemic disease was defined as UPI, which is the presence of accelerated villous maturation (AVM) or infarction. Fetal placental ischemic disease was defined as the presence of FTV. Coexistent disease was defined as the presence of both maternal and fetal placental ischemic disease.
AVM was defined as the presence of villous features at a more advanced stage than expected for gestational age. Features included an increase in syncytial knots and distal villous hypoplasia. Syncytial knots were not evaluated separately from distal villous hypoplasia. Placental infarction was defined as the presence of necrotic villi and included recent, aging, and old infarcts. The percentage of placenta infarcted was recorded (<5% or >5%). Placental disease secondary to maternal vascular underperfusion was graded with reference to previously published parameters.
Severe maternal placental ischemic disease was any placental infarction pre-34 weeks’ gestation, placental infarction greater than 5% or central placental infarction between 34 and 37 weeks’ gestation, or placental infarction greater than 20% at term (37-42 weeks’ gestation). Placental infarction of less than 5% at term was considered normal.
Mild-to-moderate maternal placental ischemic disease comprised lesser degrees of placental infarction, with variable distal villous hypoplasia and increased syncytial knots. Normal placentas did not show these features and were of normal weight for gestation.
FTV was defined as any one of the following: extensive avascular villi, hemorrhagic endovasculitis, obliterated stem arteries, or occlusive thrombi. Severe FTV was defined as 2 or more sections with over 15 villi per section showing hyalinization or stromal-vascular karyorrhexis. Cases with lesser degrees of fetal vascular obstruction were classified as mild-to-moderate disease whereas cases without any fetal vascular lesions were called “normal.”
The diagnosis of mural thrombi was made when nonocclusive fibrin aggregates were identified adherent to the luminal aspect of fetal vessels. The diagnosis of occlusive thrombi was made when at least 80% of the vessel lumen cross-sectional area was occupied by a thrombus. The presence of fresh blood or clot behind the placenta (retroplacental hemorrhage [RPH] or thrombosis) was recorded.
Chorioamnionitis was classified as acute and was staged as minimal/mild (stage I/II), moderate (stage III), or severe (stage IV). Delayed villous maturation was defined as reduced vascularization of the chorionic villi with decreased vasculosyncytial membranes. Villitis was graded from 1 to 4. For the purposes of this study, grade 1 and grade 2 villitis were grouped as low grade, whereas grade 3 and grade 4 were grouped as high-grade disease.
The criteria for suspicion of fetal placental ischemic disease included: fetal growth restriction (FGR), 1 abnormal biophysical profile, a nonreassuring cardiotocograph or in utero fetal demise. The biophysical profile was considered abnormal if oligohydramnios (<2 cm vertical pocket of amniotic fluid), decreased fetal breathing movements (absent or no episode of fetal breathing >20 seconds), decreased fetal movements (absent or <2 discrete movements), or abnormal fetal tone were present.
A nonreassuring cardiotocograph was reduced baseline variability of less than 5 beats per minute over 40 minutes, persistent early decelerations (of >15 beats per minute lasting for 15 seconds), or the presence of variable or late decelerations.
The maternal and fetal outcome were reviewed. Maternal age, parity, ethnicity, alcohol use, cigarette smoking, and previous operative delivery were obtained from the hospital database. Maternal alcohol and cigarette smoking are recorded after direct questioning by a midwife at the maternal booking visit. Maternal outcome parameters included maternal disease, the requirement for fetal growth assessment by ultrasound, fetal growth parameters on ultrasound, gestation at delivery, onset of labor, indication for induction, and mode of delivery. Our hospital operates under the Mastership system where 1 clinician (a medical Chief Executive Officer) is responsible for clinical management. Hospital management guidelines for maternal disease are based on best practice guidelines produced by the Royal College of Obstetricians and Gynaecologists.
Fetal outcome parameters include birthweight, cord pH (where available), Apgar score, Neonatal Intensive Care Unit (NICU) admission, duration of NICU stay, and perinatal outcome. Fetal growth restriction (FGR) was defined as delivery of an infant less than the 10th percentile for gestational age and sex. Severe FGR was defined as fetal birthweight less than the 3rd percentile.
Data analysis was undertaken using the Statistical Package for the Social Sciences (version 15.0; SPSS Inc, Chicago, IL). Normality was assessed with the Kolmogoroff-Smirnoff test. Frequencies, ranges, means, and medians were used to describe the findings. The χ 2 analysis was used to compare proportions. Odds ratios are presented to compare the odds of an event happening between 2 groups in bivariate analysis. The comparison of means between groups was carried out using t tests and f tests as appropriate. The Mann-Whitney and Kruskall-Wallis tests were used in place of the t test and f test, respectively, for nonparametric variables.
Results
In total, 511 cases of either UPI or FTV were identified giving a rate of 7/1000 births. Fifty-two cases were excluded because of multiple births or incomplete data and a further 13 cases were excluded because of fetal anomaly. The remaining 459 cases comprised the study group. Of the study group, 305 women were primiparous and 154 were multiparous.
The study group was further subdivided into those where placental disease was suspected antenatally based on the maternal or fetal condition (n = 324, 70.6%) and those where placental disease was diagnosed after delivery in the absence of either maternal or fetal clinical indicators (n = 135, 29.4%). The group in which placental disease was suspected antenatally was subdivided into cases where the predominant concern was maternal disease or fetal disease. In 10 cases (2.2%) more than 1 indication for intervention existed, therefore in these cases the primary medical concern was taken.
The incidence of maternal and fetal disease in the study and the indication for ultrasound in which warranted is outlined in Table 1 . Table 2 outlines the maternal characteristics of both groups. Primipara accounted for 44.2% of our delivery population over the study period. In total 69.2% (n = 310) of our study population were primiparous. There was also a statistically higher incidence of primiparous women in the group in which placental disease was suspected antenatally (71.9% vs 60.7%; P = .013).
