Spectral Doppler Parameters of Fetal Main Branch Pulmonary Artery at 20 to 40 Weeks of Gestation: Reference Ranges and Percentile Calculators.

BACKGROUND: The published reference ranges for Doppler parameters of the fetal pulmonary artery (PA) are usually derived from small sample sizes with no practical standard score or percentile ranking, which hinders systematic comparisons of Doppler figures across different gestational ages (GAs). This study aimed to establish comprehensive reference ranges and provide a percentile ranking solution for key spectral Doppler parameters. METHODS: This is a cross-sectional study of 465 uncomplicated singleton pregnancies during 20 to 40 weeks of gestation. Spectral waveforms of the fetal main branch PA were obtained with a pulsed-wave Doppler interrogation site within 5 mm from the vascular origin. Fifteen spectral Doppler parameters were identified. Associations between these parameters with GA and fetal heart rate were assessed and used to develop percentile calculators via different statistical models. The root mean squared error of each model was calculated to determine the best performance solution. RESULTS: Acceptable spectral waveforms were obtained for 94.1% (438/465) of the fetuses. All Doppler parameters except pulsatility index, manually traced pulsatility index, peak systolic velocity, and time to systolic notch/acceleration time ratio were significantly correlated with GA, while acceleration time, ejection time, time to systolic notch, peak early-diastolic reversal flow, and peak early-diastolic reversal flow/peak systolic velocity ratio were additionally significantly correlated with fetal heart rate. Support vector machine models with radial basis kernel yield the best percentile estimation (root mean squared error of 2.17-4.08 and R2 of >0.98). Furthermore, the top 5% and bottom 5% outliers could be identified with positive predictive values of 0.71 to 0.97. An online user interface of percentile calculators is available at https://github.com/cmb-chula/fetoPAD. CONCLUSIONS: This study presents normal reference ranges and percentile calculators for 15 spectral Doppler parameters of the fetal main branch PA, some of which have not been published. The estimated percentiles enhance comparison and outlier detection of the spectral Doppler figures among fetuses at different GAs.

Treatment of obstructive sleep apnea in high risk pregnancy: a multicenter randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) during pregnancy is a risk factor for preeclampsia possibly through a link to placental physiology. This study evaluates the efficacy of continuous positive airway pressure (CPAP) on the modulation of blood pressure and the reduction in preeclampsia in women with high-risk pregnancy and OSA. METHODS: A multicenter open-label, randomized controlled trial comparing CPAP treatment versus usual antenatal care was conducted in three academic hospitals in Bangkok, Thailand. Participants included singleton pregnant women aged older than 18 years with any high-risk condition (i.e., chronic hypertension, obesity, history of preeclampsia or gestational diabetes in the previous pregnancy, or diabetes), and OSA (respiratory disturbance index 5-29.99 events/hour by polysomnography), who presented either in the first trimester (gestational age, GA 0-16 weeks) or subsequently developed OSA during the 2nd trimester (GA 24-28 weeks). The primary endpoint was blood pressure during antenatal care. Secondary endpoints included the incidence of preeclampsia. An intention-to-treat analysis was performed with additional per-protocol and counterfactual analyses for handling of nonadherence. RESULTS: Of 340 participants, 96.5% were recruited during the first trimester. Thirty participants were later excluded leaving 153 and 157 participants in the CPAP and usual-care groups for the modified-intention-to-treat analysis. CPAP adherence rate was 32.7% with average use of 2.5 h/night. Overall, CPAP treatment significantly lowered diastolic blood pressure (DBP) by - 2.2 mmHg [95% CI (- 3.9, - 0.4), p = 0.014], representing approximately - 0.5 mmHg per hour of CPAP use [95%CI (- 0.89, - 0.10), p = 0.013]. CPAP treatment also altered the blood pressure trajectory by continuously lowering DBP throughout pregnancy with mean differences (95% CI) of - 3.09 (- 5.34, - 0.93), - 3.49 (- 5.67, - 1.31) and - 3.03 (- 5.20, - 0.85) mmHg at GA 18-20, 24-28, and 32-34 weeks, respectively compared to 0-16 weeks. Preeclampsia rate was 13.1% (20/153 participants) in the CPAP and 22.3% (35/157 participants) in the usual-care group with a risk difference (95% CI) of - 9% (- 18%, - 1%, p-value = 0.032) and a number-needed-to-treat (95% CI) of 11 (1, 21). CONCLUSIONS: CPAP treatment in women with even mild-to-moderate OSA and high-risk pregnancy demonstrated reductions in both DBP and the incidence of preeclampsia. CPAP treatment also demonstrated a sustained reduction in DBP throughout gestation. Trial registration ClinicalTrial.GovNCT03356106, retrospectively registered November 29, 2017.

Droplet-based digital PCR for non-invasive prenatal genetic diagnosis of α and ß-thalassemia.

Non-invasive prenatal diagnosis (NIPD) of isolated cell-free DNA from maternal plasma has been applied to detect monogenic diseases in the fetus. Droplet digital PCR (ddPCR) is a sensitive and quantitative technique for NIPD. In the present study, the development and evaluation of ddPCR-based assays for common α and ß-thalassemia variants amongst the Asian population was described; specifically, Southeast Asian (SEA) deletion, HbE, and 41/42 (-CTTT). SEA is caused by deletion of a 20 kb region surrounding the α-globin gene, whilst HbE and 41/42 (-CTTT) are caused by point mutations on the ß-globin gene. Cell-free DNA samples from 46 singleton pregnant women who were carriers of these mutations were isolated and quantified using ddPCR with specially designed probes for each target allele. Allelic copy number calculation and likelihood ratio tests were used to classify fetal genotypes. Classification performances were evaluated against ground truth fetal genotypes obtained from conventional amniocentesis. Copy number variation analysis of SEA deletion accurately classified fetal genotypes in 20 out of 22 cases with an area under the receiver operating characteristic curve of 0.98 for detecting Hb Bart's hydrops fetalis. For HbE cases, 10 out of 16 samples were correctly classified, and three were inconclusive. For 41/42 (-CTTT) cases, 2 out of 8 were correctly classified, and four were inconclusive. The correct genotype was not rejected in any inconclusive case and may be resolved with additional ddPCR experiments. These results indicate that ddPCR-based analysis of maternal plasma can become an accurate and effective NIPD for SEA deletion α-(0) thalassemia. Although the performance of ddPCR on HbE and 41/42 (-CTTT) mutations were not sufficient for clinical application, these results may serve as a foundation for future works in this field.

Effects of domperidone on augmentation of lactation following cesarean delivery at full term.

OBJECTIVE: To evaluate the effects of domperidone on breast milk production in women who underwent cesarean at full term. METHODS: Women who underwent uncomplicated full-term cesarean were randomly assigned to receive domperidone or placebo for 4 consecutive days post partum. Breast milk was collected twice daily via electric breast pump. Baseline milk production was determined by measuring the volume of milk collected on the 1st postpartum day, before initiation of study medication (day 0). The daily volume of milk collected was compared between groups. Adverse treatment-related effects were recorded. RESULTS: The study was completed by 22 women in the domperidone group and 23 in the placebo group. Compared with day 0, mean increases in milk volume per participant collected on days 1, 2, 3, and 4 were significantly higher in the domperidone (13.6 ± 23.2 mL, 68.5 ± 71.9 mL, 144.5 ± 122.3 mL, and 191.3 ± 136.1 mL) than in the placebo (2.5 ± 4.6 mL, 24.5 ± 26.5 mL, 72.1 ± 55.6 mL, and 91.4 ± 60.3 mL) group. Minor adverse effects were reported by 7 women in the domperidone group. CONCLUSION: Postpartum treatment with domperidone can augment breast milk production after full-term cesarean, with minimal adverse effects.

Eleven fetal echocardiographic planes using 4-dimensional ultrasound with spatio-temporal image correlation (STIC): a logical approach to fetal heart volume analysis.

BACKGROUND: Theoretically, a cross-sectional image of any cardiac planes can be obtained from a STIC fetal heart volume dataset. We described a method to display 11 fetal echocardiographic planes from STIC volumes. METHODS: Fetal heart volume datasets were acquired by transverse acquisition from 200 normal fetuses at 15 to 40 weeks of gestation. Analysis of the volume datasets using the described technique to display 11 echocardiographic planes in the multiplanar display mode were performed offline. RESULTS: Volume datasets from 18 fetuses were excluded due to poor image resolution. The mean visualization rates for all echocardiographic planes at 15-17, 18-22, 23-27, 28-32 and 33-40 weeks of gestation fetuses were 85.6% (range 45.2-96.8%, N = 31), 92.9% (range 64.0-100%, N = 64), 93.4% (range 51.4-100%, N = 37), 88.7%(range 54.5-100%, N = 33) and 81.8% (range 23.5-100%, N = 17) respectively. CONCLUSIONS: Overall, the applied technique can favorably display the pertinent echocardiographic planes. Description of the presented method provides a logical approach to explore the fetal heart volumes.

Maternal periodontal disease and risk of preeclampsia: a case-control study.

BACKGROUND: We examined whether pregnant women with periodontal disease have an increased risk of preeclampsia, and we empirically evaluated the extent to which associations between periodontal disease and preeclampsia are dependent upon diagnostic criteria used to define periodontal disease operationally. METHODS: One hundred and fifty preeclampsia cases and one-fifty normotensive controls who delivered a singleton infant at term were enrolled. Periodontal examinations were performed within 48 h after delivery. Participants' periodontal health status was classified, a priori, into four categories according to the extent and severity of periodontal disease. Putative risk factors for periodontal disease and preeclampsia were ascertained during in-person postpartum interviews using a structured questionnaire and by medical record abstraction. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: No clinically meaningful differences were observed between cases and controls with regard to periodontal parameters. After controlling for known confounders, severe clinical periodontal disease was not associated with an increased risk of preeclampsia (OR = 0.92, 95% CI: 0.26-3.28). In addition, there was no evidence of a linear increase in risk of preeclampsia with increasing severity of periodontal disease (P for trend = 0.65). When different diagnostic criteria previously used in other studies were used, the prevalence of periodontal disease varied substantially. However, the magnitude and direction of associations between periodontal disease and preeclampsia were largely similar regardless of the diagnostic criteria used to define periodontal disease. CONCLUSIONS: This study provides no convincing evidence that periodontal disease is associated with preeclampsia risk among Thai women.

Is maternal periodontal disease a risk factor for preterm delivery?

Several studies have suggested an association between maternal periodontal disease and preterm delivery, but this has not been a consistent finding. In 2006-2007, the authors examined the relation between maternal periodontal disease and preterm delivery among 467 pregnant Thai women who delivered a preterm singleton infant (<37 weeks' gestation) and 467 controls who delivered a singleton infant at term (> or =37 weeks' gestation). Periodontal examinations were performed within 48 hours after delivery. Participants' periodontal health status was classified into 4 categories according to the extent and severity of periodontal disease. Logistic regression was used to estimate odds ratios and 95% confidence intervals. Preterm delivery cases and controls were similar with regard to mean probing depth, mean clinical attachment loss, and mean percentage of sites exhibiting bleeding on probing. After controlling for known confounders, the authors found that severe clinical periodontal disease was not associated with an increased risk of preterm delivery (odds ratio = 1.20, 95% confidence interval: 0.67, 2.16). In addition, there was no evidence of a linear increase in risk of preterm delivery or its subtypes associated with increasing severity of periodontal disease (P(trend) > 0.05). The results of this case-control study do not provide convincing evidence that periodontal disease is associated with preterm delivery or its subtypes among Thai women.