Sonographic and genetic findings in a case of asymptomatic spontaneous uterine rupture

Abstract

An asymptomatic 25-year-old G4P0120 with history significant for cervical insufficiency and classical cesarean delivery 12.5 months prior to conception underwent routine transabdominal ultrasound at 36w4d; umbilical cord was found to be protruding into a fluid-filled pouch extruding from the lower uterine segment. During emergent cesarean delivery, a full-thickness uterine rupture was confirmed; the fetal cranium and umbilical cord were extrauterine. Maternal genotype revealed greater than expected minor allele frequencies for several collagen genes. Maternal gene expression (mRNA) and corresponding microRNA expression of these collagen genes differed several-fold between her G3 (cervical insufficiency, classical cesarean delivery) and G4 (uterine rupture) pregnancies. This case highlights that (1) cervical insufficiency, poor myometrial wound healing, and uterine rupture may co-occur and pathophysiology may be related to collagen abnormalities and (2) asymptomatic uterine rupture can be detected sonographically, even in late pregnancy. Clinicians should remain vigilant for the possibility of uterine rupture, particularly among high-risk patients.

Letter to the Editor:

A 25-year-old G4P0120, non-Hispanic White female had a history of cervical insufficiency (CI) and classical cesarean 12.5 months prior to conception (S-Table 1). At 36w4d, she had a routine biophysical profile (8/8), normal amniotic fluid volume, and was asymptomatic. An irregular fluid pouch with umbilical cord protruding through a 2.5–3.0cm lower uterine segment myometrial defect was noted (Figures 1A and 1B). Fifty-one minutes after the last ultrasound image, Pfannensteil skin incision was made. Upon peritoneal entry, the fetal head and umbilical cord were extrauterine with fetal membranes intact. No surgical hysterotomy was required to deliver the 2485g infant. Umbilical cord gases were normal. Uterine exteriorization revealed a devitalized-appearing full-thickness myometrial defect with stellate extensions.

Figure 1A. Transabdominal ultrasound image.

The uterine defect is noted between the white arrows, measuring 2.78 centimeters in this representative image.

Figure 1B. Transabdominal ultrasound image.

With the addition of color flow Doppler, the umbilical cord is seen protruding through the full thickness uterine wall defect.

The patient enrolled in a prospective Prematurity Biobank during G3 and G4. At 16w3d (G3) and 9w5d (G4), maternal blood was collected into PaxGene DNA and RNA tubes (Qiagen, Valencia, CA). Written, informed consent for Biobank enrollment and case report publication were obtained. DNA was genotyped (Illumina Precision Medicine Array). She was heterozygous for 25/81 collagen gene single nucleotide polymorphisms (SNPs), S-Table 2. RNA and microRNA abundance were quantified (NanoString panel). Collagen gene expression was lower and regulatory microRNA expression was higher in G4 vs. G3 (S-Table 3).

Uterine rupture - rare but potentially devastating for mother and fetus - is typically diagnosed clinically (abnormal fetal heart rate, abdominal pain, vaginal bleeding).² Most uterine ruptures occur intrapartum in those with a scarred uterus. Unlabored uterine rupture is rare, and pathophysiology unclear. CI often results in pre- or peri-viable delivery.¹ This case highlights the potential overlap between a predisposition for CI and uterine rupture. Further, given her prior classical cesarean, poor wound healing may also be implicated. Unlabored uterine rupture may represent a fundamental difference in myometrial integrity or wound healing vs. labored rupture,² as evidenced by a higher risk of unlabored uterine rupture among individuals with Ehlers-Danlos Syndrome (a genetic disorder involving type 1 collagen).³ CI has been associated with maternal collagen genotypes (COL1A1 and COL3A1), Mullerian anomalies, and pelvic organ prolapse.^4,5

This patient was heterozygous for multiple SNPs within collagen genes. Many of these SNPs are intronic, but we also found differential collagen gene expression in G3 (CI, classical cesarean) compared to G4 (uterine rupture). Differences were most notable in COL1A1 and COL3A1 (higher expression in G3); expression of miRNAs controlling COL3A1 – including let-7c-5p and miR-29b-3p – were 49.7-fold and 60-fold higher in G4 vs. G3, respectively.

Though a single case is insufficient to change clinical practice, this report highlights that visualization of myometrial integrity via ultrasound is feasible in late pregnancy and should be considered even among asymptomatic patients, particularly those with a prior uterine scar. Some prior studies have shown an association between sonographic uterine thickness and subsequent uterine scar dehiscence.⁶ However, routine sonographic assessment for uterine rupture is rarely performed.

Careful myometrial inspection late in pregnancy during clinically-indicated ultrasounds and heightened clinical acumen among ‘at-risk’ patients are crucial in detecting cases of asymptomatic uterine rupture and prevent devastating perinatal outcomes.