Volume 49, Issue 4

The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women’s health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women’s cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus -dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs.

Objectives Spontaneous preterm labor is an obstetrical syndrome accounting for approximately 65–70% of preterm births, the latter being the most frequent cause of neonatal death and the second most frequent cause of death in children less than five years of age worldwide. The purpose of this study was to determine and compare to uncomplicated pregnancies (1) the frequency of placental disorders of villous maturation in spontaneous preterm labor; (2) the frequency of other placental morphologic characteristics associated with the preterm labor syndrome; and (3) the distribution of these lesions according to gestational age at delivery and their severity. Methods A case-control study of singleton pregnant women was conducted that included (1) uncomplicated pregnancies (controls, n=944) and (2) pregnancies with spontaneous preterm labor (cases, n=438). All placentas underwent histopathologic examination. Patients with chronic maternal diseases (e.g., chronic hypertension, diabetes mellitus, renal disease, thyroid disease, asthma, autoimmune disease, and coagulopathies), fetal malformations, chromosomal abnormalities, multifetal gestation, preeclampsia, eclampsia, preterm prelabor rupture of the fetal membranes, gestational hypertension, gestational diabetes mellitus, and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome were excluded from the study. Results Compared to the controls, the most prevalent placental lesions among the cases were the disorders of villous maturation (31.8% [106/333] including delayed villous maturation 18.6% [62/333] vs. 1.4% [6/442], q<0.0001, prevalence ratio 13.7; and accelerated villous maturation 13.2% [44/333] vs. 0% [0/442], q<0.001). Other lesions in decreasing order of prevalence included hypercapillarized villi (15.6% [68/435] vs. 3.5% [33/938], q<0.001, prevalence ratio 4.4); nucleated red blood cells (1.1% [5/437] vs. 0% [0/938], q<0.01); chronic inflammatory lesions (47.9% [210/438] vs. 29.9% [282/944], q<0.0001, prevalence ratio 1.6); fetal inflammatory response (30.1% [132/438] vs. 23.2% [219/944], q<0.05, prevalence ratio 1.3); maternal inflammatory response (45.5% [195/438] vs. 36.1% [341/944], q<0.01, prevalence ratio 1.2); and maternal vascular malperfusion (44.5% [195/438] vs. 35.7% [337/944], q<0.01, prevalence ratio 1.2). Accelerated villous maturation did not show gestational age-dependent association with any other placental lesion while delayed villous maturation showed a gestational age-dependent association with acute placental inflammation (q-value=0.005). Conclusions Disorders of villous maturation are present in nearly one-third of the cases of spontaneous preterm labor.

Objectives Gestational IDA has been linked to adverse maternal and neonatal outcomes, but the impact of iron supplementation on outcome measures remains unclear. Our objective was to assess the effects of gestational IDA on pregnancy outcomes and compare outcomes in pregnancies treated with either oral or intravenous iron supplementation. Methods We evaluated maternal and neonatal outcomes in 215 pregnancies complicated with gestational IDA (Hb<100 g/L) and delivered in our tertiary unit between January 2016 and October 2018. All pregnancies from the same period served as a reference group (n=11,545). 163 anemic mothers received oral iron supplementation, and 52 mothers received intravenous iron supplementation. Results Gestational IDA was associated with an increased risk of preterm birth (10.2% vs. 6.1%, p=0.009) and fetal growth restriction (FGR) (1.9% vs. 0.3%, p=0.006). The gestational IDA group that received intravenous iron supplementation had a greater increase in Hb levels compared to those who received oral medication (18.0 g/L vs. 10.0 g/L, p<0.001), but no statistically significant differences in maternal and neonatal outcomes were detected. Conclusions Compared to the reference group, prematurity, FGR, postpartum infections, and extended hospital stays were more common among mothers with gestational IDA, causing an additional burden on the families and the healthcare system.

Objectives Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. Methods Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. Results We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. Conclusions These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

Objectives We estimated the degree to which the association between race and spontaneous recurrent preterm delivery is mediated by the timing of the first prenatal care visit. Methods A retrospective population-based cohort study was conducted using the U.S. National Center for Health Statistics Natality Files. We identified 644,576 women with a prior PTB who delivered singleton live neonates between 2011 and 2017. A mediation analysis was conducted using log-binomial regression to evaluate the mediating effect of timing of first prenatal care visit. Results During the seven-year period, 349,293 (54.2%) White non-Hispanic women, 131,296 (20.4%) Black non-Hispanic women, 132,367 (20.5%) Hispanic women, and 31,620 (4.9%) Other women had a prior preterm delivery. The risk of late prenatal care initiation was higher in Black non-Hispanic women, Hispanic women, and Other women (women of other racial/ethnic backgrounds) compared to White non-Hispanic women, and the risk of preterm delivery was higher in women with late prenatal care initiation. Between 8 and 15% of the association between race and spontaneous recurrent preterm delivery acted through the delayed timing of the first prenatal care visit. Conclusions Racial disparities in spontaneous recurrent preterm delivery rates can be partly, but not primarily, attributed to timing of first prenatal care visit.

Objectives The aim of this prospective study was to correlate the Doppler ultrasonography of the uterine arteries with the Kurjak Antenatal Neurodevelopmental Test (KANET), to investigate the effect of uterine artery flow assessed by the Doppler on fetal behavior. Methods A population of 80 pregnant women in the second trimester of pregnancy was included for uterine artery Doppler (UAD) assessment. The investigation group consisted of 40 women with abnormal UAD, while the control group consisted of 40 women with normal UAD. The inclusion criteria for the investigated group were: gestation above 20 weeks, and an abnormal finding of Doppler ultrasonography of the uterine arteries. All patients underwent a KANET test and were followed up to the end of their pregnancy. Results There was a statistically significant difference in the average score of KANET tests between the two groups (9.20±3.32 vs. 13.55±2.21; p=0.001). In the first group, an abnormal flow on the side of the placenta affected the score of the KANET test (B=11.948; p=0.005), while abnormal flow on the opposite side did not affect the score of the KANET test (p>0.05). Physiological flow had no effect on the KANET test in the control group (p>0.05). Conclusions Abnormal flow affects the value of the KANET score, and can be used as one of the parameters in evaluation of probable fetal neurodevelopmental disorders.

Objectives During the last decade obesity has been continuously rising in adults in industrial countries. The increased occurrence of perinatal complications caused by maternal obesity poses a major challenge for obstetricians during pregnancy and childbirth. This study aims to examine the association between parity, pregnancy, birth risks, and body mass index (BMI) of women from Lower Saxony, Germany. Methods This retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony’s statewide quality assurance initiative. Mothers were categorized according to BMI as normal weight (18.5 to <25 kg/m 2 ) or obese (≥30 kg/m 2 ). Results Most of the mothers in this study population were either in their first (33.9%) or second pregnancy (43.4%). The mean age of women giving birth for the first time was 28.3 years. Maternal age increased with increasing parity. The proportion of pregnant women with a BMI over 30 was 11% in primiparous women, 14.3% in second para, 17.3% in third para and 24.1% in fourth para or more women. Increasing parity was positively correlated with the incidence of classical diseases related to obesity, namely diabetes mellitus, gestational diabetes, hypertension, pregnancy-related hypertension and urinary protein excretion. An increased risk of primary or secondary cesarean section was observed in the obese women, particularly during the first deliveries. Conclusions There is a positive and significant correlation between parity and increased maternal BMI. The highest weight gain happens during the first pregnancy. The rate of operative deliveries and complications during delivery is increased in obese pregnant women.

Objectives Increased placental stiffness is associated with various pathological conditions. Our objective was to evaluate the relation between the second-trimester placental elasticity value in low-risk pregnant women and poor obstetric outcomes. Methods A total of 143 pregnant women were enrolled. Placental elasticity values were measured using the transabdominal point shear wave elastography method. 10 random measurements were obtained from different areas of the placenta. The mean was accepted as the mean placental elasticity value. Logistic regression analyses were performed to identify independent variables associated with obstetric outcomes. Results Second-trimester placental elasticity value was significantly and positively associated with the poor obstetric outcomes (p=0.038). We could predict a poor outcome with 69.2% sensitivity and 60.7% specificity if we defined the placental elasticity cut-off as 3.19 kPa. Furthermore, in the multiple regression model, the placental elasticity value added significantly to the prediction of birth weight (p=0.043). Conclusions Our results showed that the pregnancies with a stiffer placenta in the second trimester were associated with an increased likelihood of exhibiting poor obstetric outcomes. Also, placental elasticity was independently associated with birth weight.

Objectives To compare the rate of fetal loss in pregnancy after second trimester amniocentesis between procedures performed by experts and non-experts and to assess other pregnancy complications as secondary outcomes. Methods A retrospective cohort study was performed on singleton pregnancies that underwent mid-trimester amniocenteses in a single institution. The fetal loss rates of procedures performed by experts and non-experts were collected and analyzed. Other adverse pregnancy outcomes were also examined. Results In total, 14,450 amniocenteses were performed during the study period. These included 11,357 (78.6%) procedures in the group expert operators and 3,093 (21.4%) procedures in the group non-expert operators. In the non-expert group, the fetal loss rate was slightly increased but not significantly (p=0.24).In addition, the higher number of spontaneous abortions was associated with blood-stained amniotic fluid sample (p<0.001; RR=9.28). Multiple needle insertions also increased in the non-expert group significantly. However, no difference in pregnancy outcomes was found between in single and multiple needle insertions. Conclusions The amniocentesis procedures performed by the non-experts was not increase the fetal loss rate. However, the other adverse pregnancy outcomes, including preterm birth, low birth weight and fetal growth restriction were significantly increased in the non-expert group.

Objectives Vitamin D plays an important role in the release of the placenta and implantation, and low levels are a risk factor for pre-eclampsia. Studies have also shown that symptomatic treatment of vitamin D3 deficiency can effectively reduce the risk of pre-eclampsia. In this study, vitamin D3 supplementation was performed on the risk of pre-eclampsia to observe its effect. Methods From January 2016 to December 2018, 450 women with maternal treatment and delivery in our hospital underwent an open-label randomized study. The pregnant women were divided into low-dose, medium-dose, and high-dose groups. Compare the incidence of pre-eclampsia and the dose effect of vitamin D levels. Results In the maternal and perinatal periods of the 450 maternal women, the 25[OH] index of the three groups of pregnant women was significantly increased, while the high-dose increase index was more obvious. The relative risk reduction rate was significantly lower. Compared with the low-dose and middle-dose groups, the high-dose group had a significantly lower incidence of pre-eclampsia, while the IUGR index was lower, and other obstetric indicators were comparable. Conclusion Vitamin D supplementation can effectively reduce the incidence of pre-eclampsia, while reducing the IUGR index, which has important value and significance in its clinical application.

Objectives The main objective of the present study was to evaluate what educational needs were being neglected in current perinatal educational program in the University of Malaga. Methods We performed a cross-sectional study using the Students’ questionnaire on attitudes towards childbirth (CAVE-st) in a sample of 378 students who were finishing their undergraduate or postgraduate academic perinatal program, including medical and nursing students. Results The Cronbach’s alpha reliability coefficient was 0.895. The mean score of CAVE-st in the sample was 200.34 (DT 21.0). The scores were below the median value in more than 53% of the students, especially in medical students. Female students scored systematically higher in the overall scale and its subscales, even after adjusting for study groups. On the other hand, the students with children scored significantly lower in the subscale that explored their attitudes towards unexpected results. A huge margin for improvement was recognizable in those subscales related with childbirth medicalization, respect to women decisions, and health-care prioritization. Conclusions Students’ attitude towards childbirth need to be improved as a means to improve women’s childbirth experience and prevent birth-related trauma. The current undergraduate and postgraduate training in perinatal care lacks a comprehensive and biopsychosocial perspective that would improve the quality of clinical practice during childbirth.

Objectives To report the normal fetal cardiac axis (CA) values at the time of the first trimester screening ultrasound. Methods Standardized images and measurement of the CA were obtained from 100 healthy fetuses between 11+0 and 13+6 weeks of gestation along with the nucal thichkness (NT), Crown–rump length (CRL) and other measurements. We excluded cases with abnormal NT, later diagnosis of abnormalities, and suspected fetal cardiopathy during the pregnancy follow-up. Data analysis was performed after all the patients delivered and cardiopathy was excluded. Results CA was measurable in all the cases. Higher CRL was associated with a decrease in the CA. The mean ± SD embryonic/fetal CA was 48±5,2°, ranging from 39 to 60°, The 2.5 percentile was defined at 40° and the 97.5 percentile at 59°. The Pearson test resulted in a significant correlation between CA and CRL with a coefficient R of 70% and p-value <0.01. Conclusions CA tends to decrease at the 11 to 13+6 gestational ages. We defined 2.5 and 97.5% curves for the normal values of CA in our Middle Eastern population. A larger study will be required to differentiate normal and abnormal values for the early detection of heart abnormalities.

Objectives To find out if the expressed breast milk delivery rate to neonatal intensive care unit (NICU) for babies who were hospitalized for any reason other than COVID-19, and exclusive breastfeeding (EB) rates between discharge date and 30th day of life of those babies were affected by COVID-19 pandemic. Methods Babies who were hospitalized before the date first coronavirus case was detected in our country were included as control group (CG). The study group was divided into two groups; study group 1 (SG1): the mothers whose babies were hospitalized in the period when mother were asked not to bring breast milk to NICU, study group 2 (SG2): the mothers whose babies were hospitalized after the date we started to use the informed consent form for feeding options. The breast milk delivery rates to NICU during hospitalization and EB rates between discharge and 30th day of life were compared between groups. Results Among 154 mother-baby dyads (CG, n=50; SG1, n=46; SG2, n=58), the percentage of breast milk delivery to NICU was 100%, 79% for CG, SG2, respectively (p<0.001). The EB rate between discharge and 30th day of life did not change between groups (CG:90%, SG1:89%, SG2:75.9; p=0.075). Conclusions If the mothers are informed about the importance of breast milk, the EB rates are not affected by the COVID-19 pandemic in short term, even if the mothers are obligatorily separated from their babies. The breast milk intake rate of the babies was lowest while our NICU protocol was uncertain, and after we prepared a protocol this rate increased.

Objectives Identifying and understanding the main risk factors associated with extubation failure of very low birthweight (VLBW) infants in different populations can subsequently help in establishing better criteria while taking decision of extubation. The aim of the study was to identify factors associated with extubation failure in VLBW infants. Methods A cohort study of VLBW infants who underwent their first extubation between April 2018 and December 2019 in a Neonatal Intensive Care Unit, Alagoas, Brazil, were included in this study. Extubation failure was defined as reintubation within seven days of extubation. Relative risks of predictive variables different between the extubation success group (ES) and extubation failure group (EF) were estimated with a robust Poisson regression model. Results Out of the 112 infants included, 26 (23%) cases exhibited extubation failure. Extremely low birth weight (RR 2.55, 95% CI 1.07, 6.06), mechanical ventilation duration for first extubation greater than seven days (RR 2.66, 95% CI 1.10, 6.45), vaginal delivery (RR 2.07, 95% CI 1.03, 4.18) and maternal chorioamnionitis (RR 4.89, 95% CI 1.26–18.98) remained independently associated with extubation failure. EF had a significant greater need for respiratory support, longer oxygen therapy duration, more bronchopulmonary dysplasia (BPD) and longer length of hospital stay, even when adjusted for confounding variables. Conclusions Extremely low birth weight infants needing mechanical ventilation, wherein the duration for first extubation was longer than seven days, with vaginal delivery and maternal chorioamnionitis failed more frequently at the first attempt of extubation. And this failure increased the risk of BPD and the length of hospital stay.

Objectives Given the adverse effects of either polycystic ovary syndrome (PCOS) or overweight/obesity, one could speculate that patients with both would fare worse than others. We sought to evaluate the relationship between pregravid BMI and pregnancy complications in PCOS patients conceived by assisted reproductive techniques (ART). Methods Maternal and fetal/neonatal outcomes of singleton pregnancies after assisted reproduction in women with and without PCOS were compared by pregravid body mass index (BMI, <24.9 vs. ≥25 kg/cm 2 ). Results The study population comprised 185 with a BMI <24.9 kg/cm 2 including 39 (21%) with PCOS and 146 (79%) without. We also included 84 patients with BMI ≥25 kg/cm 2 , involving 34 (40.5%) with PCOS and 50 (59.5%) without. PCOS (total 73 patients) was significantly more common among overweight/obese patients, OR 2.5 (95% CI 1.4, 4.4). Neonates >4,000 g were born only to the overweight/obese mothers in the PCOS group. A higher incidence of gestational diabetes, chronic hypertension, and gestational hypertension was related to pregravid overweight/obesity rather than PCOS. Conclusions In this specific subgroup of patients conceived after assisted reproduction, pregravid BMI>25 kg/cm 2 rather than PCOS itself appears to be associated with GDM and hypertensive disorders.

Objectives To examine whether audio-voice guidance application improves adherence to resuscitation sequence and recommended time frames during neonatal resuscitation. Methods A prospective, randomized, pilot study examining the use of an audio-voice application for guiding resuscitation on newborn mannequins, based on the Neonatal Resuscitation Program (NRP) algorithm. Two different scenarios, with and without voice guidance, were presented to 20 medical personnel (2 midwives, 8 nurses, and 10 physicians) in random order, and their performance videotaped. Results Audio-voice guided resuscitation compared with non-guided resuscitation, resulted in significantly better compliance with NRP order sequence (p<0.01), correct use of oxygen supplementation (p<0.01) and performance of MR SOPA (Mask, reposition, suction, open mouth, pressure, airway) (p<0.01), and shortened the time to “positive pressure ventilation” (p<0.01). Conclusions In this pilot study, audio-voice guidance application for newborn resuscitation simulation on mannequins, based on the NRP algorithm, improved adherence and performance of NRP guidelines.