Impact of tocolysis-intent magnesium sulfate and beta-adrenergic agonists on perinatal brain damage in infants born between 28-36 weeks' gestation.

AIMS: Magnesium sulfate has neuroprotective effects in preterm infants. Whether other antepartum treatments interfere with the neuroprotective actions is not well known. This study aims to explore the impacts of antenatal administration of Magnesium sulfate or beta-2 adrenergic agonists as tocolytic agents on the developing brain in premature infants. METHODS: This is a retrospective cohort study in four tertiary perinatal centers in Japan. We collected data of pregnant women and infants born between 28 and 36 weeks for tocolytic agents, gestational age, sex, antenatal corticosteroid, fetal growth restriction, pathological chorioamnionitis, low umbilical arterial pH values (<7.1), multiple pregnancy, mode of delivery and institutions after excluding clinical chorioamnionitis, non-reassuring fetal status or major anomalies. Tocolytic agents were categorized into four groups: no-tocolysis, magnesium sulfate, beta-2 adrenergic agonists and the combination of them. We conducted multiple comparisons with multivariate analyses using generalized linear regression models to compare the prevalence of a poor perinatal outcome defined as infant's death, brain damage, particularly cerebral palsy and developmental delay. RESULTS: Among 1083 infants, 39% were no-tocolysis, 47% were magnesium sulfate, 41% were beta-2 adrenergic agonists and 27% were combination group, including the duplication. The incidence of poor perinatal outcome was decreased by magnesium sulfate (OR 0.27, 95% CI 0.10-0.72), but not changed significantly by beta-2 adrenergic agonists (OR 1.28, 95% CI 0.63-2.59) or the combination group (OR 2.24, 95% CI 0.67-7.54), compared with the no-tocolysis. CONCLUSION: The combination therapy for tocolysis with beta-2 adrenergic agonists diminished the magnesium sulfate neuroprotective action after adjusting for covariables.

A multiple regression model for predicting a high cytomegalovirus immunoglobulin G avidity level in pregnant women with IgM positivity.

OBJECTIVE: To establish a model to predict high cytomegalovirus (CMV) immunoglobulin (Ig)G avidity index (AI) using clinical information, to contribute to the mental health of CMV-IgM positive pregnant women. METHODS: We studied 371 women with IgM positivity at ≤14 w of gestation. Information on the age, parity, occupation, clinical signs, IgM and G values, and IgG AI was collected. The IgG AI cut-off value for diagnosing congenital infection was calculated based on a receiver operating characteristic curve analysis. Between-group differences were assessed using the Mann-Whitney U-test or χ2 analysis. The factors predicting a high IgG AI were determined using multiple logistic regression. RESULTS: The women were divided into high or low IgG AI groups based on an IgG AI cut-off value of 31.75. There were significant differences in the IgG and IgM levels, age, clinical signs, and the number of women with one parity between the two groups. In a multiple logistic regression analysis, IgM and the number of women with one parity were independent predictors. This result helped us establish a mathematical model that correctly classified the IgG AI level for 84.6% of women. CONCLUSION: We established a highly effective model for predicting a high IgG AI immediately after demonstrating IgM positivity.

Delayed rhythm formation of normal-structured, growth-restricted fetuses using fetal heart rate monitoring patterns.

AIMS: Growth-restricted fetuses have delayed rhythm formation in utero. The awake-sleep cycle of fetal heart rate pattern is thought to represent fetal rhythm. We aimed to study if the emergence of rhythm formation on fetal heart rate pattern delays in fetal growth restriction compared to appropriate-for-date fetuses. METHODS: This was a retrospective cohort study including 75, normal-structured, singleton fetuses. Of them, 21 were fetal growth restriction and the remaining 54 were appropriate-for-date infants. We examined timing of emergence of rhythm formation on fetal heart rate pattern comparing between fetal growth restriction and appropriate-for-date fetuses after adjusting possible confounding factors as outcome measures. RESULTS: Rhythm formation was significantly delayed in fetal growth restriction (<10th percentile) compared to the appropriate-for-date subgroups (10-30, 30-50, 50-70 and 70-90th percentile) by 1-2 weeks. After adjusting confounding factors, growth restriction was the only independent variable to delay fetal rhythm formation. One infant for each group had neurodevelopmental disorder and the incidence did not reach statistically significant. CONCLUSION: Based on fetal heart rate pattern analysis, growth-restricted fetuses show 1-2 weeks delay in rhythm formation compared to appropriate-for-date fetuses.

A case of mirror syndrome caused by hydrops fetalis after fetoscopic laser photocoagulation.

Fetoscopic laser photocoagulation (FLP) of placental anastomoses is a well-established procedure for twin-to-twin transfusion syndrome that improves fetal outcome with rare maternal complications. However, fetal hydrops can develop even after FLP, and mirror syndrome can occur, indicating that both the fetal and maternal courses should be monitored after FLP.

Circadian Variation in the Onset of Placental Abruption.

Objective. To determine circadian variation in the onset of placental abruption. Methods. A retrospective study involving 115 placental abruptions, divided into four subgroups based on initial symptoms comprising abdominal pain, vaginal bleeding, both abdominal pain and bleeding, or other symptoms. The time of the initial symptom was considered the disease onset. We analyzed the frequency of disease onset and adverse perinatal outcome including perinatal death relative to the daily four 6-hour intervals. Results. Abdominal pain displayed significant circadian variation regarding the period of onset with higher levels from 0:00 AM to 6:00 AM (65%) compared with 0:00 PM to 6:00 PM (24%, p < 0.01). Vaginal bleeding did not display significant circadian variation (p = 0.45). Adverse perinatal outcome showed significant circadian variation with a higher occurrence of perinatal death from 0:00 AM to 6:00 AM (35%) compared with 0:00 PM to 6:00 PM (0%, p < 0.01). After adjustment using variables of abdominal pain and time period, both variables significantly affected perinatal death (odds ratio: 13.0 and 2.2, resp.). The risk of adverse perinatal outcome increased significantly when abdominal pain occurred, except for the period 0:00 PM to 6:00 PM (OR, 9.5). Conclusion. Placental abruption beginning with abdominal pain has circadian variation.

Antithrombin improves the maternal and neonatal outcomes but not the angiogenic factors in extremely growth-restricted fetuses at <28 weeks of gestation.

AIMS: Severe preterm fetal growth restriction (FGR) remote from term is problematic. We aimed to investigate the effect of maternally-administered antithrombin on maternal and neonatal outcomes. A prospective, one-arm, pilot study was performed in 14 women with severe FGR (≤5th centile) at <28 weeks of gestation, without hypertensive disorders. Maternal plasma concentrations of soluble Feline McDonough Sarcoma (FMS)-like trypsin kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured and categorized into three groups: group 1; low sFlt-1 and high PlGF, group 2; moderate sFlt-1 and low PlGF, and group 3; high sFlt-1 and low PlGF. Antithrombin was administered for 3 days. The incidence of perinatal mortality, infant morbidity, and the period of pregnancy prolongation were compared. RESULTS: In group 1 (n=4), their pregnancies were extended for longer periods and the maternal and infant outcomes were good. The prolongation periods were shorter in groups 2 (n=3) and 3 (n=7), which resulted in poor maternal [severe preeclampsia or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome] and infant outcomes. CONCLUSIONS: The evaluation of the maternal sFlt-1 and PlGF at 21-27 weeks of gestation is useful in the managements of severe FGR. Antithrombin treatment could prolong the pregnancies with low sFlt-1 and high PlGF without negatively affecting maternal or fetal health.

Maternal immunoglobulin G avidity as a diagnostic tool to identify pregnant women at risk of congenital cytomegalovirus infection.

BACKGROUND: The immunoglobulin (Ig) G avidity index (AI) is useful to detect primary cytomegalovirus (CMV) infection. However, because IgG matures with time, this index is not useful to detect a primary infection, unless measured at an appropriate time. OBJECTIVES: We aimed to clarify the difference between using IgG AI and IgM positivity according to the stage of pregnancy to identify congenital CMV infection risk. STUDY DESIGN: We collected the serum samples from 1115 pregnant women who underwent maternal screening for primary infection (n = 956) and were referred to our hospital because of CMV IgM positivity (n = 155) or had abnormal fetal ultrasonography findings (n = 4). The same sera samples were used to measure CMV IgM, IgG, and IgG AI. An IgG AI of <35% was defined as low. Neonatal urine collected within 5 days after birth was examined by polymerase chain reaction to confirm congenital infection. RESULTS: Fourteen mothers gave birth to infected neonates. The sensitivity, specificity, and negative predictive values of the low IgG AI group with IgM-positive samples to discriminate between women with congenital infection at ≤14 weeks of gestation were 83.3, 83.8, and 99.1, respectively, which were higher than those of other subjects. Uni- and multivariate analyses revealed that IgM positivity and low IgG AI were independent variables associated with congenital infection at any stage of pregnancy, except low IgG AI at ≥15 weeks of gestation. CONCLUSION: Low IgG AI with IgM positivity at ≤14 weeks of gestation was a good indicator of congenital infection, which should prove useful in obstetric practice.