Screening vs no screening for preterm delivery in low risk singleton pregnancies

Introduction: To compare the effect of a policy of screening for spontaneous preterm delivery (SPD) by transvaginal cervical length (CL) measurement versus a no screening policy in the prevention of severe prematurity. Methods: Retrospective study on low risk singleton pregnancies examined at 20-24 weeks. Two cohorts one with SPD screening and the other without screening were matched using propensity analysis to create the study groups. Women with short CL were treated with vaginal progesterone and/or cervical cerclage/pessary. The outcomes examined were SPD<32 weeks (SPD 32) and SPD between 20 and 32 weeks (SPD 20-32). Results: Screening for SPD was associated with a significant reduction in the rate of SPD at less than 32 weeks (0.3% vs 0.8%, p=0.001 in the screened and no screened pregnancies respectively) and in the rate of SPD 20-32 (0.3% vs 0.9%, p=0.005 in the screened and no screened pregnancies respectively). After adjusting for maternal age, parity, body mass index, smoking and mode of conception, the screening group had significantly lower hazard for SPD 20-32 (HR=0.36, 95% CI: 0.18-0.75, p=0.006) and SPD32 (HR=0.39, 95% CI: 0.19-0.82, p=0.013). Conclusion: Screening for SPD by transvaginal CL measurement in mid pregnancy may reduce the incidence of severe prematurity in low risk singleton pregnancies.

Spontaneous preterm delivery is reflected in both early neonatal and maternal gut microbiota

Background Aberrant gut microbiota composition in preterm neonates is linked to adverse health consequences. Little is known about the impact of perinatal factors or maternal gut microbiota on initial preterm gut colonization. Methods Fecal samples were collected from 55 preterm neonates (<35 gestational weeks), 51 mothers, and 25 full-term neonates during the first 3–4 postpartum days. Gut microbiota composition was assessed using 16S ribosomal RNA gene sequencing. Results Preterm neonates exhibited significantly lower gut microbiota alpha diversity and distinct beta diversity clustering compared to term neonates. Spontaneous preterm birth was associated with distinct initial gut microbiota beta diversity as compared to iatrogenic delivery. Gestational age or delivery mode had no impact on the preterm gut microbiota composition. The cause of preterm delivery was also reflected in the maternal gut microbiota composition. The contribution of maternal gut microbiota to initial preterm gut colonization was more pronounced after spontaneous delivery than iatrogenic delivery and not dependent on delivery mode. Conclusions The initial preterm gut microbiota is distinct from term microbiota. Spontaneous preterm birth is reflected in the early neonatal and maternal gut microbiota. Transmission of gut microbes from mother to neonate is determined by spontaneous preterm delivery, but not by mode of birth. Impact The initial gut microbiota in preterm neonates is distinct from those born full term. Spontaneous preterm birth is associated with changes in the gut microbiota composition of both preterm neonates and their mothers. The contribution of the maternal gut microbiota to initial neonatal gut colonization was more pronounced after spontaneous preterm delivery as compared to iatrogenic preterm delivery and not dependent on delivery mode. Our study provides new evidence regarding the early gut colonization patterns in preterm infants. Altered preterm gut microbiota has been linked to adverse health consequences and may provide a target for early intervention.

The amniotic fluid cell-free transcriptome in spontaneous preterm labor

The amniotic fluid (AF) cell-free RNA was shown to reflect physiological and pathological processes in pregnancy, but its value in the prediction of spontaneous preterm delivery is unknown. Herein we profiled cell-free RNA in AF samples collected from women who underwent transabdominal amniocentesis after an episode of spontaneous preterm labor and subsequently delivered within 24 h (n = 10) or later (n = 28) in gestation. Expression of known placental single-cell RNA-Seq signatures was quantified in AF cell-free RNA and compared between the groups. Random forest models were applied to predict time-to-delivery after amniocentesis. There were 2385 genes differentially expressed in AF samples of women who delivered within 24 h of amniocentesis compared to gestational age-matched samples from women who delivered after 24 h of amniocentesis. Genes with cell-free RNA changes were associated with immune and inflammatory processes related to the onset of labor, and the expression of placental single-cell RNA-Seq signatures of immune cells was increased with imminent delivery. AF transcriptomic prediction models captured these effects and predicted delivery within 24 h of amniocentesis (AUROC = 0.81). These results may inform the development of biomarkers for spontaneous preterm birth.

Antibody microarray analysis of the amniotic fluid proteome for predicting the outcome of rescue cerclage in patients with cervical insufficiency

Little is known about the biomarkers that can identify patient candidates suitable for rescue cerclage procedure. The purpose of the study was to identify novel biomarkers in amniotic fluid (AF) that can predict the outcome of rescue cerclage in patients with cervical insufficiency by using an antibody microarray. This case-control study was conducted using AF samples collected from singleton pregnant women who underwent rescue cerclage following a diagnosis of cervical insufficiency (19–25 weeks). Patients were divided into case (n=20) and control (n=20) groups based on the occurrence of spontaneous preterm delivery (SPTD) at &lt;34 weeks of gestation after cerclage placement. The AF proteomes were analyzed using an antibody microarray for biomarker discovery work. Ten candidate biomarkers of interest were validated by ELISA. Thirty-one of the molecules studied showed significant intergroup differences (≥ 2-fold change in signal intensity). Validation by ELISA confirmed significantly higher levels of APRIL, S100 A8/A9, TIMP-1, MIP-1α, and IL-8 in women who had SPTD at &lt;34 weeks. Of these, AF S100 A8/A9 and TIMP-1 levels were independent of other potentially confounding factors (e.g., cervical dilatation). S100 A8/A9 had the highest area under the curve at 0.857. Using protein–antibody microarray technology, we identified differentially expressed proteins and several novel biomarkers (APRIL, IL-8, MIP-1α, S100 A8/A9, and TIMP-1) in AF from women who had SPTB at &lt;34 weeks after cerclage for cervical insufficiency. These data can provide an insight into the molecular mechanisms underlying SPTD after rescue cerclage in patients with cervical insufficiency.

Primary biliary cholangitis: a rare diagnosis during pregnancy

Primary biliary cholangitis is an autoimmune disease that mostly affects women. It is uncommon in women of childbearing age and the diagnosis during pregnancy is rare and can be challenging. Described here is a case of primary biliary cholangitis first manifesting during pregnancy, with the onset of pruritus, jaundice, biochemical liver abnormalities and positive antimitochondrial antibodies. Although treatment with ursodeoxycholic acid was started at the time of diagnosis, there was a progressive worsening of cholestatic biochemical markers throughout pregnancy. In addition, fasting hyperglycemia with polyhydramnios was diagnosed, consistent with gestational diabetes. She had a spontaneous preterm delivery at 31 weeks of gestation, of a newborn who was admitted to the neonatal intensive care unit but who subsequently had no long-term sequelae of preterm delivery. A maternal postpartum flare occurred. Treatment with ursodeoxycholic acid was well tolerated during pregnancy and lactation.

Valsartan exposure in pregnancy with resultant anhydramnios and chronic kidney disease in a late preterm infant

In utero exposure to angiotensin II receptor blockers (ARBs) has fetotoxic effects including renal failure, oligohydramnios and lung hypoplasia. We present the case of a 24-year-old woman who presented to the maternity services in the 34th week of her first pregnancy. She was taking valsartan for hypertension. Ultrasound showed a structurally normal fetus with anhydramnios. The patient was admitted and valsartan was discontinued. She had spontaneous preterm delivery at 35 weeks’ gestation of a baby girl. The baby’s urine output was minimal in the first week of life and she was transferred to a paediatric hospital for specialist nephrology input. At 6 months of age, she requires ongoing nephrology follow-up and she remains on treatment for hypertension and anaemia. This case demonstrates the serious adverse effects resulting from ARB exposure in utero, and highlights the importance of avoiding fetotoxic medications in women of childbearing age.