Volume 48, Issue 7

Objectives To compare the fetal and maternal outcomes in surviving singletons of vanishing twin, with singletons or twins, in pregnancies following assisted reproductive technology (ART). Content We searched the PubMed, Embase, Web of Science and Cochrane databases from the time of conception of the database until Dec 2019 to identify relevant published studies. Perinatal outcomes were synthesized with random effects meta-analysis using RevMan 5.3. Summary and Outlook Fifteen studies were included. Dichorionic twin pregnancies conceived by ART wherein the vanishing twin phenomenon occurred had a risk of fetal malformation similar to that of ART singleton pregnancies (OR=1.25; 95% CI 0.87–1.79) and a higher risk of fetal malformation compared with ART twin pregnancies (OR=1.82; 95% CI 1.23–2.70). Moreover, the remaining fetus in ART vanishing twin pregnancy was at a significantly higher risk of preterm birth (<37 weeks) compared to fetuses in ART singleton pregnancies (OR=2.41; 95% CI 1.46–3.99) and a markedly lower risk of preterm birth (<37 weeks) compared to the fetuses in ART twin pregnancies (OR=0.19; 95% CI 0.16–0.22). Meanwhile, the risk of delivery of infants who were small for gestational age (SGA) was significantly higher in ART vanishing twin pregnancies compared to that in ART singleton pregnancies (OR=2.70; 95% CI 1.39–5.24) and similar to that in ART twin pregnancies (OR=0.67; 95% CI 0.27–1.65). The risks of preterm birth and of the infant being SGA is higher for the remaining fetus in an ART vanishing twin pregnancy compared to those for the fetuses in ART singleton pregnancies; the risk of fetal malformation is also higher in such cases compared with ART twin pregnancies.

Cervical insufficiency (CI) is a mainly disease leading to recurrent abortions and preterm birth which may present in about 1% of obstetric populations. Recurrent pregnancy losses caused by CI incur serious economic burdens on society as well as huge psychological burdens to family members. However, many patients even clinicians in some areas of the world still remain confused about this disease. At the same time, the etiology of CI is still uncertain and it is still a controversial disease in diagnosis and treatment. This article summarizes the potential risk factors associated with CI, which could be worthy of attention and helpful for future research. It also reviews the methods for diagnosis and treatment of CI to better understand this noteworthy disease, as well as presents the related consensus and controversies according to the newly updated guidelines, which has practical significance for conducting more in-depth investigations in the future.

Objectives Measurement of birth length and birth head circumference is part of the newborn assessment. Both measurements aid in distinguishing between proportionate and disproportionate small and large for gestational age newborns. It had been shown that birth weight is related to maternal height and weight. This study aims to analyze birth length and birth head circumference percentiles based on maternal stature. Methods This observational study analyzed birth length and birth head circumference percentiles of 2.3 million newborns stratified by maternal height and weight from the first obstetric assessment. Percentiles were calculated for sex and 22–43 gestational weeks for all infants. Eighteen subgroups based on six maternal height and three weight strata were defined and percentiles calculated from 32 to 42 gestational weeks using GAMLSS package for R. Results Newborns of mothers with height <158 cm and weight <53 kg (short stature) had a rate of preterm birth of 9%, compared to 5% in the tall stature group (height >177 cm, weight >79 kg). Small stature mothers were 1.7 years younger. Birth length differed by several centimeters for the same percentiles between groups of short and tall stature mothers, whereas birth head circumference differed up to 1.2 cm. The largest deviation of birth length was between the 97th percentiles. For male newborns born at term, birth length at the 97th percentile differed by 3.2 cm, at the 50th percentile by 2.7 cm and at the third percentile by 2.5 cm. Conclusions Birth length and birth head circumference are related to maternal height and weight. To more completely assess newborns, the maternal size should be considered.

Objectives A sonographic short cervix is one of the strongest predictors of preterm delivery. However, the cellular immune composition of amniotic fluid in women with a short cervix has not yet been described. Herein, we determined cellular and soluble immune responses in amniotic fluid from pregnant women with a mid-trimester asymptomatic short cervix. Methods Amniotic fluid samples (n=77) were collected from asymptomatic women with a cervical length between 15 and 25 mm (n=36, short cervix) or ≤15 mm (n=41, severely short cervix) diagnosed by ultrasound. Flow cytometry and multiplex measurement of cytokines/chemokines were performed. Results (1) The cellular immune composition of amniotic fluid did not differ between women with a severely short cervix (≤15 mm) and those with a short cervix 15–25 mm; (2) amniotic fluid concentrations of multiple cytokines/chemokines were higher in women with a severely short cervix (≤15 mm) than in those with a short cervix 15–25 mm; (3) the cellular immune composition of amniotic fluid did not differ between women with a severely short cervix (≤15 mm) who ultimately underwent preterm delivery and those who delivered at term; and (4) amniotic fluid concentrations of IL-2, but not other immune mediators, were increased in women with a severely short cervix (≤15 mm) who ultimately delivered preterm compared to those who delivered at term. Conclusions Women with a severely short cervix (≤15 mm) have increased concentrations of pro-inflammatory mediators in the amniotic cavity; yet, these do not translate to changes in the cellular immune response.

Objectives To compare pregnancy outcomes with medication assisted treatment using. methadone or buprenorphine in term mothers with opioid use disorder. Methods A cohort of women receiving medication assisted treatment with either methadone or buprenorphine were identified from delivery records over a 10‐year period. Women were excluded with delivery <37 weeks, multiple gestations, or a known anomalous fetus. Maternal demographics, medications, mode of delivery, birthweight, newborn length of stay, and neonatal abstinence syndrome were extracted. The study was IRB approved and a p-value of <0.05 was significant. Results There were 260 women, 140 (53.8%) with methadone use and 120 (46.2%) with buprenorphine use. Groups were similar for maternal age, race, parity, homeless rate, tobacco use, mode of delivery and incidence of neonatal abstinence syndrome. The methadone group had a lower mean newborn birthweight (2874±459 g) and a greater incidence of low birth weight (11.4%) than the buprenorphine group (3282±452 g; p<0.001 and 2.5%; p=0.006). The incidence of neonatal abstinence syndrome was similar between groups (97% methadone vs. 92.5% buprenorphine; p=0.08). The methadone group had a longer newborn length of stay (11.4+7.4 days) and more newborn treatment with morphine (44.6%) than the buprenorphine group (8.2+4.4 days; p<0.001 and 24.2%; p<0.001). Maternal methadone use was an independent predictor for a newborn length of hospital stay >7 days (OR 3.61; 95% confidence interval 1.32–9.86; p=0.01). Conclusions Medication assisted treatment favors buprenorphine use when compared to. methadone with an increased birthweight, reduced need for newborn treatment, and a shorter newborn length of stay in term infants.

Objectives Aim of the study was to analyze the impact of head circumference (HC) and birth weight (BW) on the delivery mode and delivery outcomes. Methods Study population consisted of pregnancy, delivery and newborn data from 1,762 women, who delivered between 2004 and 2016 at University Hospital of Zurich (UHZ). Odds ratio (OR) with 95% confidence intervals (CI) were calculated for mode of delivery. Newborns were sorted into four groups according HC or BW. To evaluate the association between HC and delivery outcome, a descriptive analysis was performed. In addition reference charts of newborn HC at term were constructed. Results OR for instrumental delivery (ID) was 2.37 (CI 95%, 1.63–3.46), for C-Section (CS) 3.74 (CI 95%, 1.49–9.37) when HC >36 cm. OR for ID was 1.59 (CI 95%, 1.02–2.50), for CS 3.18 (CI 95% 1.08–9.350) when BW was >4,000 g. OR for ID was 2.15 (95% CI, 1.69–2.73), for CS 1.93 (95% CI, 0.89–4.18) when HC ≥36 cm and BW <4000 g. OR for ID was 2.23 (95% CI, 1.35–3.67), for CS 4.39 (95% CI, 1.48–12.99) when HC ≥36 cm and BW ≥4,000 g. HC ≥36 cm was defined as large in our study. Mothers with higher age and body mass index delivered babies with larger HC (p<0.05). Blood loss and duration of expulsion period and BW was associated with larger HC (p<0.05). Conclusions The rate of ID and CS increased in case of a larger HC and greater BW. However, the main prognostic factor for ID was size of HC: ≥36 cm, but not macrosomia.

Objectives Our aim was to study the association of clinical variables obtainable before delivery for severe neonatal outcomes (SNO) and develop a clinical tool to calculate the prediction probability of SNO in preterm prelabor rupture of membranes (PPROM). Methods This was a prospective study from October 2015 to May 2018. We included singleton pregnancies with PPROM and an estimated fetal weight (EFW) two weeks before delivery. We excluded those with fetal anomalies or fetal death. We examined the association between SNO and variables obtainable before delivery such as gestational age (GA) at PPROM, EFW, gender, race, body mass index, chorioamnioitis. SNO was defined as having at least one of the following: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, or neonatal death. The most parsimonious logistic regression models was constructed using the best subset selection model approach, and receiver operator curves were utilized to evaluate the prognostic accuracy of these clinical variables for SNO. Results We included 106 pregnancies, 42 had SNO (39.6%). The EFW (area under the receiver operating characteristic curve [AUC]=0.88) and GA at PPROM (AUC=0.83) were significant predictors of SNO. The addition of any of the other variables did not improve the predictive probability of EFW for the prediction of SNO. Conclusions The EFW had the strongest association with SNO in in our study among variables obtainable before delivery. Other variables had no significant effect on the prediction probability of the EFW. Our findings should be validated in larger studies.

Objectives The purpose of this study is to compare the vacuum extractor cup application technique described by Bird vs. the technique described by Vacca on a simulation model. Methods Six obstetricians participated in the study. Each obstetrician performed eight vacuum assisted deliveries using the Bird technique and eight vacuum assisted deliveries using the Vacca 5-Steps technique. Results A total of 96 vacuum assisted deliveries were performed. The mean distance from the centre of the cup to the flexion point was 1.78±0.96 cm for the Bird technique and 1.05±0.60 cm for the Vacca technique (p<0.001). The lateral distance (over the parietal bone) was 1.16±0.69 cm for the Bird technique and 0.66±0.52 cm for the Vacca technique (p<0.001). The vertical distance (towards the frontal or occipital bone) was 1.12±1.02 cm for the Bird technique and 0.67±0.55 cm for the Vacca technique (p=0.009). In occipito anterior positions, there were no significant differences between both techniques. Conclusions The Vacca technique was better in transverse and posterior positions.

Objectives Pregnant women are more susceptible to certain infections; however, this increased susceptibility is not fully understood. Herein, systems biology approaches were utilized to elucidate how pregnancy modulates tissue-specific host responses to a bacterial product, endotoxin. Methods Pregnant and non-pregnant mice were injected with endotoxin or saline on 16.5 days post coitum (n=8–11 per group). The uterus, cervix, liver, adrenal gland, kidney, lung, and brain were collected 12 h after injection and transcriptomes were measured using microarrays. Heatmaps and principal component analysis were used for visualization. Differentially expressed genes between groups were assessed using linear models that included interaction terms to determine whether the effect of infection differed with pregnancy status. Pathway analysis was conducted to interpret gene expression changes. Results We report herein a multi-organ atlas of the transcript perturbations in pregnant and non-pregnant mice in response to endotoxin. Pregnancy strongly modified the host responses to endotoxin in the uterus, cervix, and liver. In contrast, pregnancy had a milder effect on the host response to endotoxin in the adrenal gland, lung, and kidney. However, pregnancy did not drastically affect the host response to endotoxin in the brain. Conclusions Pregnancy imprints organ-specific host immune responses upon endotoxin exposure. These findings provide insight into the host-response against microbes during pregnancy.

Objectives To evaluate the effects of nifedipine treatment on fetal hemodynamics and cardiac function during preterm labor. This prospective study assessed several quantitative parameters of fetal cardiac circulation and function, and found no significant changes at 48 h after nifedipine treatment. These findings suggest that tocolytic nifedipine may be safe for fetuses. It supports clinicians to use nifedipine treatment for tocolysis without any cardiac effect on the fetus. Methods A prospective cohort study was conducted at a tertiary hospital between January 2016 and October 2017. A total of 45 pregnant women who required nifedipine for preterm labor were included in this study. Fetal Doppler ultrasound was performed and fetal systolic and diastolic function was measured prior to, and 48 h after, the first nifedipine treatment. Conventional Doppler parameters were used to evaluate fetal heart function and hemodynamic changes. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion and the sphericity index were also evaluated to assess changes in fetal cardiac morphology. Results No significant changes in fetal Doppler parameters were observed following nifedipine tocolysis. There was no significant difference in the fetal cardiac function parameters of both ventricles before vs. after nifedipine treatment. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, and sphericity index values were unchanged following nifedipine treatment. Conclusions Oral administration of nifedipine did not to alter fetal cardiac function or morphology. Fetal cardiac parameters and various Doppler indices were unchanged following nifedipine treatment. Maternal nifedipine treatment does not appear to have any significant effect on fetal cardiac function.

Objectives Violence against medical trainees confronts medical educators and academic leaders in perinatal medicine with urgent ethical challenges. Despite their evident importance, these ethical challenges have not received sufficient attention. The purpose of this paper is to provide an ethical framework to respond to these ethical challenges. Methods We used an existing critical appraisal tool to conduct a scholarly review, to identify publications on the ethical challenges of violence against trainees. We conducted web searches to identify reports of violence against trainees in Mexico. Drawing on professional ethics in perinatal medicine, we describe an ethical framework that is unique in the literature on violence against trainees in its appeal to the professional virtue of self-sacrifice and its justified limits. Results Our search identified no previous publications that address the ethical challenges of violence against trainees. We identified reports of violence and their limitations. The ethical framework is based on the professional virtue of self-sacrifice in professional ethics in perinatal medicine. This virtue creates the ethical obligation of trainees to accept reasonable risks of life and health but not unreasonable risks. Society has the ethical obligation to protect trainees from these unreasonable risks. Medical educators should protect personal safety. Academic leaders should develop and implement policies to provide such protection. Institutions of government should provide effective law enforcement and fair trials of those accused of violence against trainees. International societies should promulgate ethics statements that can be applied to violence against trainees. By protecting trainees, medical educators and academic leaders in perinatology will also protect pregnant, fetal, and neonatal patients. Conclusions This paper is the first to provide an ethical framework, based on the professional virtue of self-sacrifice and its justified limits, to guide medical educators and academic leaders in perinatal medicine who confront ethical challenges of violence against their trainees.

Objectives MR compatible incubators (MRcI) offer the examination of preterm and critically ill infants in controlled environment. The aim of the study was to compare objective and subjective image quality as well as diagnostic value of MRI brain examinations with and without using the MRcI. Thus, predictive value of brain MRI at expected delivery date in general was investigated. Methods This retrospective study included MRI brain examinations conducted at patients’ corrected age ≤6 months and presence of four standard sequences (PD TSE transversal, T2 TSE transversal, T2 TSE sagittal and T1 SE transversal). Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR) was calculated. Subjective image quality was estimated using a 5-point Likert scale. Findings of MRI were compared with those of previous transfontanellar ultrasound because of additional diagnostic information. Severe brain abnormality scaled by score of Kidokoro was related to results of Munich Functional Developmental Diagnostics (MFDD) within first year. Results One hundred MRI brain examinations (76 with MRcI, 24 without MRcI) were performed in 79 patients. Using the MRcI SNR and CNR were significantly higher in PD- and in T2-weighted sequences (p<0.05). TSE PD transversal demonstrated a higher risk of non-diagnostic quality using MRcI (OR 5.23; 95%-CI 1.86–14.72). MRcI revealed additional diagnostic information (OR 5.69; 95%-CI 1.15–28.24). Severe brain abnormality was associated with walking deficits (r=0.570; p=0.021). Conclusions The MRcI increased objective image quality and revealed additional diagnostic information to transfontanellar ultrasound. Nevertheless, prediction of infants' future development remains limited.

Objectives Recombinant human erythropoietin (rhEPO) has been shown to effectively and safely prevent the anemia of prematurity and to reduce the transfusion need in very low birth weight (VLBW) infants and has been licensed for this indication in Europe in 1997. The objective of the study was to obtain information on the use or non-use of rhEPO in neonatal units in Germany and other European countries. Methods Anonymized 14-questions web-based questionnaire. Results Seventy-nine questionnaires from Germany and 63 questionnaires from other 15 European countries were completed. Of the responders, 39% indicated to use rhEPO routinely or occasionally in VLBW infants, whereas 61% responded to never use rhEPO in this population. The major reasons given for non-use were lack of recommendation in national guidelines (69%) and/or doubt about efficacy of rhEPO to reduce transfusion need (53%). Twenty-seven percent of the responders indicated to use rhEPO for neonates with birth weights above 1,500 g. Neuroprotection in VLBW infants (26%) and hypoxic ischemic encephalopathy in term neonates (27%) were given as indications for off label use of rhEPO. Conclusions This survey indicates that rhEPO is used for the anemia of prematurity as licensed in less than half of neonatal units in Germany and other European countries. On the other hand it seems to be used off label in neonates for neuroprotection in a considerable number of units although there is no final evidence on its neuroprotective effects.

Objectives To identify the probability of survival and severe neurodevelopmental impairment (sNDI) at which perinatal physicians would or would not offer or recommend resuscitation at birth for extremely preterm infants. Methods A Delphi process consisting of five rounds was implemented to seek consensus (>80% agreement) amongst British Columbia perinatal physicians. The first-round consisted of neonatal and maternal-fetal-medicine Focus Groups. Rounds two to five surveyed perinatal physicians, building upon previous rounds. Draft guidelines were developed and agreement sought. Results Based on 401 responses across all rounds, consensus was obtained that resuscitation should not be offered if survival probability <5%, not recommended if survival probability 5 to <10%, resuscitation recommended if survival without sNDI probability >70 to 90% and resuscitation standard care if survival without sNDI >90%. Conclusions This physician consensus-based, objective framework for the management of an anticipated extremely preterm infant is a transparent alternative to existing guidelines, minimizing gestational-ageism and allowing for individualized management utilizing up-to-date data. Further input from other key stakeholders will be required prior to guideline implementation.