Introduction
Preterm birth (PTB) is the most significant reason for neonatal mortality and morbidity. It is called preterm birth if delivery occurs in less than 37 weeks of gestation. One of the major steps in preterm birth prevention is risk assessment. In about two-thirds of cases, preterm birth is spontaneous; in the other one-third of cases, it occurs due to medical issues like fetal growth restriction, preeclampsia, etc. Preterm babies are more likely to have short-term morbidities like intracranial hemorrhage, respiratory problems, necrotizing enterocolitis, patent ductus arteriosus, infection, etc. Due to the multiple etiologies linked to PTB, prediction and prevention are challenging.
What Are the Risk Factors for Preterm Birth?
The risk factors include the following:
Maternal Risk Factors:
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Ethnicity - Some studies show ethnic differences in PTB risk.
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Maternal BMI (Body Mass Index) - extremely low or high pre-pregnancy BMI of the mother may increase the risk of PTB.
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Smoking - Smoking during pregnancy increases PTB risk.
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The Periodontal Disease of the Mother - The mother’s periodontal disease is linked to spontaneous PTB. This is due to the hematogenous spread of inflammatory mediators like cytokines and pathogens.
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Maternal Infections - An alkaline vaginal pH due to infections like bacterial vaginosis increases the risk of PTB. Urogenital infections also increase the risk of preterm birth.
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Vitamin D Deficiency - Some studies have shown an association between vitamin D deficiency in the mother and an increased risk of PTB.
Obstetric History:
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Previous PTB History - A previous PTB history can increase the risk of recurrence.
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Curettage in History - Women who have previously undergone miscarriages or terminations previously managed by cervical dilatation and curettage are at an increased risk for spontaneous PTB.
Maternal History:
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Previous Excisional Cervical Procedures - Women who have undergone excisional procedures for cervical dysplasia are at increased risk of PTM.
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Uterine Anomalies - women with uterine anomalies like a uterine septum, a bicornuate uterus, etc., are at increased risk of PTB.
Issues Related to Current Pregnancy:
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Multiple Gestations - Women with multiple babies are at increased risk.
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Pregnancy Interval- Shorter and longer pregnancy intervals are linked to a greater risk of PTB.
How Do Ultrasound Markers Play a Role in PTB Prediction?
Cervical Length Screening:
Cervical length screening using transvaginal ultrasound is a good predictor of preterm birth risk in singleton pregnancies.
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In women with a singleton pregnancy and no prior history of PTB, a shorter cervical length during the mid-trimester increased the risk of spontaneous PTB.
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In women with uterine anomalies, a cervical length of fewer than twenty-five millimeters is linked with PTB of less than 35 weeks.
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In women with multiple pregnancies without prior PTB history, a cervical length of less than 25 mm in mid-trimester is linked with an increased risk of PTB.
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Short cervical length was an independent risk factor for preterm birth.
Cervical Consistence Analysis:
The cervix also undergoes structural changes during labor. These changes can be assessed using two methods that analyze cervical elastography. These are shear wave elastography and strain elastography. These, when combined with cervical length measurement, help in PTB prediction.
Newer Methods:
During the second trimester, an increase in the uterocervical angle, which is the angle between the cervical canal and the lower uterine segment, was associated with an increased risk of preterm birth.
The placental strain ratio, which is determined using sonoelastography, is found to be an effective predictor of preterm birth.
What Is the Role of Biomarkers in Preterm Birth Prevention?
Maternal Serum Markers:
Maternal serum calponin 1 is a biomarker used for the short-term prediction of preterm birth. Some studies have suggested that the ratio of maternal serum alpha-fetoprotein/ amniotic fluid alpha-fetoprotein is a good predictor of preterm delivery. Maternal salivary estriol detected during 25 to 34 weeks of gestation was a negative predictor for identifying those women who do not deliver preterm.
Amniotic Fluid:
Those mothers who underwent amniocentesis during 16 to 22 weeks of gestation and were found to have a low amniotic fluid glucose level were linked with preterm delivery. An increase in VEGF (vascular endothelial growth factor) and placental growth factor at sixteen to nineteen weeks of pregnancy predict preterm birth.
Cervical Fluid:
Fetal fibronectin is a glycoprotein that is usually found in cervicovaginal fluid before 22 weeks of pregnancy. Still, if it is found in the cervicovaginal fluid between 24 to 34 weeks of pregnancy, then it indicates a risk of PTB.
Saliva:
According to certain studies, a low salivary progesterone level between 24 to 34 weeks of pregnancy is described as a risk for PTB.
Urine:
There is insufficient data to support the correlation between biomarkers in urine and the risk of preterm birth. However, urine analysis is done to screen pregnant women with asymptomatic bacteremia for antibiotic administration, reducing the risk of developing infection-associated preterm birth.
Blood:
Though blood can be easily assessed, allowing for rapid sampling, due to its comparatively large volume, the chemical biomarkers present may be diluted among the vast amount of serum proteins.
What Are Future Approaches to Preterm Labor Prediction?
The detection of a single biomarker and its use to predict spontaneous preterm labor pose an important challenge due to the various biochemical mechanisms involved. Diagnostic efficacy can be improved by quantifying more than one biochemical marker. Certain studies that analyzed the ability to predict preterm birth within three days using the interleukin-1 family of cytokines found that a combined model that used all three cytokines showed an increased sensitivity of around 86 percent compared to individual markers with a sensitivity of around 52 percent.
Conclusion
Accurate prediction and prevention of preterm birth remain significant challenges modern obstetrics faces. Proper risk assessment helps tailor the interventions and therapeutic medications aimed at improving fetal and maternal outcomes. Along with maternal risk factor assessment, screening tools like cervical length assessment, ultrasound markers, and biomarkers effectively predict preterm birth.
