Chorionic Villus Sampling, Early Amniocentesis, and Termination of Pregnancy Without Diagnostic Testing: Comparison of Fetal Risk Following Positive Non-invasive Prenatal Testing.

BACKGROUND: With the increased accuracy of non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) techniques, the likelihood of false-positive screening results has been reduced for high-risk populations. Following a positive screening test, a diagnostic procedure to confirm the result is strongly recommended, although some patients have terminated pregnancies because of a positive NIPT alone. Chorionic villus sampling (CVS), the diagnostic procedure of choice in the first trimester, is not available in all locations. Amniocentesis before 15 weeks, referred to as early amniocentesis (EA), is associated with a 1% rate of talipes and an increased rate of early pregnancy loss compared with CVS. Our objective was to compare the level of risk for euploid pregnancies following a positive NIPT based on the invasive procedure chosen. METHOD: Using data from a 2003 meta-analysis, we estimated the rates of adverse pregnancy outcome in euploid pregnancies based on the positive predictive value (PPV) of NIPT and the invasive procedure used-that is, CVS, EA, or termination of pregnancy (TOP). RESULTS: Following NIPT, we found that the rate of adverse fetal outcomes in euploid pregnancies was lower for CVS than for EA at all PPV levels. As the PPV of NIPT increased, the difference in risk between EA and CVS decreased. The risk to euploid pregnancies of TOP was excessive at all PPVs. CONCLUSION: CVS is the recommended diagnostic test in the first trimester because it is safer than EA for the fetus. However, EA is better than no testing when early TOP is planned. Patients should be strongly counselled against TOP without confirmatory testing.

Effect of taurocholic acid on fetoplacental arterial pressures in a dual perfusion placental cotyledon model: a novel approach to intrahepatic cholestasis of pregnancy.

OBJECTIVE: To determine if continuous infusion of taurocholic acid into the fetoplacental and intervillous circulation of a placental cotyledon affects the fetal arterial pressure response after injection of the thromboxane mimetic U44619. Taurine conjugated bile acid is one bile acid putatively mediating intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: We selected 5 placentas from normal, unlabored patients. Two cotyledons from each placenta were isolated and dually perfused. Taurocholic acid was continuously infused into the fetoplacental and intervillous circulation of the test cotyledon. After 30 minutes U44619 was injected into both the test and control cotyledon vascular circuits. Pressure excursions were measured and compared to baseline pressures using a paired Student's t test. RESULTS: There was significant attenuation of the pressure excursion in the cotyledons perfused with taurocholic acid as compared to controls after injection of U44619. The difference from baseline in the taurocholic cotyledon compared with controls was 44.2 mmHg vs. 71.8 mmHg (p = 0.009). CONCLUSION: The perfusion of taurocholic acid attenuated the pressure response to thromboxane mimetic U44619 in the fetoplacental arterial circulation of a placental cotyledon as compared to control. This finding in our ex-vivo model may represent changes that occur in the placental vasculature with intrahepatic cholestasis of pregnancy. These placentas may have dysregulated vascular tone, which could contribute to the adverse fetal effects observed in ICP.

Interaction between maternal obesity and Bishop score in predicting successful induction of labor in term, nulliparous patients.

OBJECTIVE: Determine the Bishop score most predictive of induction of labor (IOL) success for different maternal weight groups. STUDY DESIGN: Retrospective cohort study. Prospectively collected database utilized to determine the optimum Bishop score within each prepregnancy body mass index (BMI) category of term, nulliparous patients undergoing IOL. RESULTS: For the total group (n = 696), Bishop score ≥ 5 was most predictive of success (75% versus 56%, p < 0.0001). Within each BMI category, Bishop score ≥ 5 remained most predictive: normal weight (79% versus 64%, p < 0.01); overweight (72% versus 58%, p = 0.03); and obese (73% versus 45%, p < 0.0001). Overall, nonobese patients had more success than obese patients (70% versus 59%, p < 0.01). The nonobese group had more success than the obese group when the Bishop score was < 3 (57% versus 39%, p < 0.05) but not when it was ≥ 3 (72% versus 65%, p = 0.1). Also, there was a higher fraction of patients with Bishop score < 3 in the obese group compared with the nonobese group (25% versus 14%, p < 0.001). CONCLUSION: The optimum Bishop score for predicting successful IOL in nulliparous patients was 5 regardless of BMI class. The higher IOL failure rate observed in obese women was associated with lower starting Bishop scores and was compounded by higher failure rates in obese women with Bishop scores < 3.

Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors.

We sought to determine if maternal use of selective serotonin reuptake inhibitors (SSRIs) in the second half of pregnancy is associated with persistent pulmonary hypertension of the newborn (PPHN). We performed a case-controlled study (1:6 ratio) of infants delivered at Madigan Army Medical Center with primary PPHN from 2003 through 2009. Study and control patients were compared for the following clinical factors: SSRI use after 20 weeks gestation, mode of delivery, maternal disease, body mass index, tobacco use, fetal gender, maternal age, and parity. We identified 20 cases of primary PPHN out of 11,923 births for an incidence of 0.17%. Mode of delivery was the only factor we found to be associated with PPHN. Specifically, cesarean delivery (CD) prior to the onset of labor increased the risk for PPHN: odds ratio (OR) = 4.9, confidence interval (CI) 1.7 to 14.0. Importantly, use of SSRIs in the second half of pregnancy was identified in 5% of the controls but none of the cases (OR = 0, CI 0 to 3). PPHN is associated with CD prior to the onset of labor but not with SSRI use in the second half of pregnancy. Previous studies linking PPHN to SSRI use relied on after-the-fact patient interviews and incomplete records. Additional studies are needed to verify these results.

The effect of magnesium sulfate on the activity of matrix metalloproteinase-9 in fetal cord plasma and human umbilical vein endothelial cells.

OBJECTIVE: Clinical evidence suggests that magnesium sulfate may reduce the risk of fetal neurologic injury in preterm delivery. Matrix metalloproteinase-9 (MMP-9) levels are elevated in preterm labor patients. There is evidence that MMP-9 may break down the blood-brain barrier in humans, causing cytokine mediated cell injury. Our objective was to determine whether the addition of magnesium sulfate attenuates activity of MMP-9, a complex zinc-dependent enzyme, in fetal cord plasma. STUDY DESIGN: We collected cord plasma in 6 term, unlabored patients. Using enzyme-linked immunosorbent assay, we measured the activity of MMP-9 with varying concentrations of magnesium sulfate added in vitro. Results were verified using a human umbilical cord vein endothelial cell (HUVEC) line. RESULTS: Addition of physiologic doses of magnesium sulfate (0.07 mg/mL) resulted in a 25% decrease in active MMP-9 (P = .03). In a HUVEC line, magnesium sulfate resulted in a 32% decrease in MMP-9 activity (P = .00012). CONCLUSION: The addition of magnesium sulfate attenuated MMP-9 activity in cord plasma and in a HUVEC line.

The pregnancy "super-utilizer": how does a high-risk depression screen affect medical utilization?

OBJECTIVE: Our objective was to determine whether a score of >11 on the Edinburgh postnatal depression scale (EPDS) at the initial prenatal visit was associated with an increased use of acute medical visits when compared to pregnant women with an initial EPDS score of ≤11. METHODS: This was a retrospective cohort study comparing the utilization of acute medical care during pregnancy and the first eight weeks after delivery amongst 200 women with an EPDS score >11 at their initial prenatal visit compared with 200 women with an EPDS score ≤11. "Super-utilization" was defined as ≥4 acute or unscheduled medical visits during pregnancy and the first eight weeks after delivery (90th percentile). Logistic regression was used to control for confounders. RESULTS: Women with an initial EPDS score >11 were significantly more likely to engage in super-utilization of acute medical care compared with those women scoring ≤11 (adjusted odds ratio [aOR], 2.12; 95% confidence interval [CI], 1.53-3.90). CONCLUSIONS: Pregnant women scoring >11 on the EPDS at their initial prenatal visit are more likely to super-utilize acute medical care in the perinatal period. This subset of patients at-risk for increased utilization can be identified early during prenatal care. Interventions to better meet the medical and psychosocial needs of these women warrant future research.

Micronized progesterone reduces vasoconstriction in the placenta.

OBJECTIVE: To investigate if micronized progesterone (P4) has the ability to attenuate thromboxane mimetic U46619-mediated fetoplacental artery vasoconstriction. METHODS: Paired cotyledons obtained from the same placenta of five-term subjects were analyzed. The fetal artery and maternal intervillous space of one cotyledon was infused with P4 while another cotyledon was infused with control perfusate. After 30 min, a bolus dose of U44619 was administered to both cotyledons. RESULTS: The change in the measured fetoplacental vascular pressure caused by bolus administration of U46619 was less in the cotyledons infused with P4 (p = 0.009). CONCLUSION: Continuous treatment with P4 significantly attenuates the U46619-mediated fetoplacental vasoconstriction.

Effect of dexamethasone administered with magnesium sulfate on inflammation-mediated degradation of the blood-brain barrier using an in vitro model.

Patients at risk for preterm delivery are frequently administered both antenatal steroids for fetal maturation and magnesium sulfate for neuroprotection. In this study, we investigate whether steroids coadministered with magnesium sulfate preserve blood-brain barrier integrity in neuroinflammation. Human umbilical vein endothelial cells were grown in astroglial conditioned media in a 2-chamber cell culture apparatus. Treatment with tumor necrosis factor-α (TNF-α) or catalytically active recombinant matrix metalloproteinase 9 (MMP-9) simulated neuroinflammation. Membrane integrity was assessed by zona occludens 1 (ZO-1) immunoreactivity, permeability to fluorescently conjugated dextran, and transendothelial electrical resistance (TEER). The TNF-α and MMP-9 treatment increased the rate of dextran transit, decreased TEER, and decreased ZO-1 immunoreactivity at junctional interfaces. Dexamethasone pretreatment alone or in combination with 0.5 mmol/L magnesium sulfate preserved monolayer integrity after inflammatory insult. Magnesium sulfate alone was not protective. This study supports a possible interaction between steroids and magnesium in neuroprotection.