The current study describes the natural course of LLP diagnosed early in pregnancy and suggests a new model for predicting persistent cases. To the best of our knowledge, this is the first report regarding a cohort that includes only women with LLP. The executive summary of the joint Fetal Imaging Workshop recommended ultrasound evaluation at 16 weeks of gestation to rule out placenta previa. In cases of LLP, a follow-up ultrasound is recommended at 32 weeks of gestation 7. The routine practice of fetal anomaly surveys in Israel includes early anomaly scan at 13–16 weeks of gestation and second trimester anomaly scan at 21–24 weeks. This provides a window of opportunity to investigate the clinical behavior and natural course of different types of placentation over a range of gestational ages, as described in this study.
According to our results, we can define phases of resolution that divide pregnancies with LLP into three categories, with different clinical characteristics. The small group of persistent LLP had unique characteristics compared to the other two groups. These included significantly older maternal age, earlier gestational age at delivery, higher second trimester hCG levels, shorter cervical lengths measured during first and second trimester anatomy scans and higher rate of peripartum complications. The combination of these findings defines persistent LLP pregnancies as high-risk pregnancies in contrast to cases of LLP that resolve during pregnancy.
Therefore, the challenge of managing early diagnosis of LLP is to detect the cases that will persist until delivery, early. To meet this challenge, we present a novel predictive model for persistent LLP that uses two statistically significant clinical parameters—early second trimester cervical length and second trimester hCG. By utilizing this linear SVM classification, the predictive accuracy of the model was 90.3% (5-fold Cross-Validation was used. The parameters of cervical length and beta hCG measurements used in this model are easily detected as part of routine pregnancy follow-up.
The clinical implications of this novel model enable us to detect a high-risk population of women with persistent low-lying placenta as early as the first anatomy scan and the second trimester hCG level evaluation. Early detection will improve the follow-up and management of these women and will reduce stress and uncertainty among all women with LLP.
Regarding the natural course of LLP detected early in pregnancy, we found that most cases resolved by 21–24 weeks of gestation. About half of the persistent cases resolved in the third trimester and only 9.5% persisted until delivery.
Previous studies reported that placenta previa diagnosed in the mid-trimester resolved in 66–98% of cases and the resolution is more likely with LLP 4,8. The process of resolution is termed migration. There are various hypotheses considering the etiology of migration. One of these is trophotropism, the process of atrophy of thin placental margins due to a poor vascular supply in the lower uterine segment 1,9. Another theory is dynamic placentation, in which it is hypothesized that the anterior uterine wall expands more than the posterior wall. This can relate to possibly higher migration rate of anterior placentas because the lower uterine segment will lengthen due to elongation and hypertrophy during pregnancy, causing the uterus to enlarge on the anterior side1. The migration process might explain our results. In cases of migration failure, LLP will persist.
Earlier studies that tried to approach this subject were heterogenous and included cases of LLP and complete placenta previa in the same study group1–4, 8,10. Durst et al. reported 91.9% resolution of LLP or placenta previa among 1,663 pregnant women at the mid-trimester anatomy survey.1 The median time to resolution was 10 weeks. The probability of resolution was inversely proportional to the distance from the internal os. However, this finding is limited because the distance of the placenta from the internal cervical os was known in only 51% of women. Our findings in the selected population with LLP are consistent with these results.
Alouini et al.2 found that complete placenta previa and most placentas less than 1 cm from the internal cervical os did not migrate. Most cases with placentas located more than 1 cm away, migrated three to four weeks later. They used 1 cm from internal cervical os as a cutoff value.
The trend toward shorter cervix and earlier delivery in Group 3 may reflect negative effects of persistent LLP on the cervix. This might be explained by abnormal vascular changes due to the lower placentation.
Pathological placentation is a term used to describe an abnormal location of the placenta, abnormal invasion of the placenta into the uterine wall, or both11. Increased levels of biological markers, such as hCG in maternal serum are thought to result from early placental vascular damage and possibly be due to their greater absorption into maternal blood flow 11. Berezowsky et al. found that second trimester hCG levels were significantly higher among cases of pathological placentation, such as those in the spectrum of placenta previa and placenta accreta12. Interestingly, we found higher levels of hCG the longer the LLP persisted. This can be due to abnormal placentation and is used as a marker in our suggested model.
Peripartum maternal bleeding is another well-known complication of low placentation. Our results revealed that persistent LLP is a risk-factor for heavier bleeding and lower postpartum hemoglobin levels. Therefore, labor involving persistent LLP should be managed carefully, blood products should be appropriately prepared and careful intra- and postpartum clinical surveillance should be performed.
The main limitation of the current study lies in its retrospective design. Nevertheless, it has several important strengths. First, all data were collected from a single center with uniform management protocols and all measurements were performed by the same sonographer. Moreover, the relatively large sample of patients with LLP without placenta previa is unique.
In conclusion, a new model for detecting persistent LLP is presented in this study. Most cases of LLP diagnosed at early anomaly scan resolve before delivery. Persistence versus resolution of LLP may represent two different clinical entities and not a resolution spectrum of the same clinical condition. The longer the persistence, the less likely it will resolve. Those who persisted until delivery were associated with unique clinical characteristics including shorter cervical length, high second trimester hCG level and maternal complications, which partially may be explained by a different pathophysiology of the placentation process. These characteristics can be recognized as soon as the low placentation is diagnosed and may serve as a predictive factor for non-resolution, with an accuracy of 90%, as seen in the predictive model. This can increase physician awareness regarding the need for closer surveillance. These findings are very important for obstetricians managing LLP during pregnancy and in the delivery room and while consulting with patients and making shared decisions throughout the pregnancy.