The risk of perinatal mortality with each week of expectant management in obese pregnancies

Introduction: The risk of stillbirth associated with maternal obesity increases with gestational age; however, it is unclear if earlier delivery reduces the overall perinatal mortality rate. Our objective was to compare the risk of perinatal mortality associated with each additional week of expectant management to that of immediate delivery.

Methods: This was a retrospective cohort study of singleton non-anomalous births in Texas between 2006 and 2011. Analyses were stratified based on maternal pre-pregnancy BMI class. For each BMI class, we calculated the rate of neonatal death and stillbirth at each week of gestation from 34 to 41 weeks. A composite risk of perinatal mortality associated with 1 week of expectant management was estimated combining the stillbirth rate of the current week and the neonatal death rate of the following week. This was compared with the rate of neonatal death of the current week.

Results: After all exclusions, 2,149,771 births remained for analysis. In the normal weight group, stillbirth risk increased from 0.8 per 10,000 births at 34 weeks to 5.7 per 10,000 births at 42 weeks, whereas the neonatal death risk decreased from 76.5 per 10,000 births at 34 weeks to 30.4 per 10,000 births at 42 weeks, there were no differences between expectant management and delivery for any gestational week. In the obese group, stillbirth risk increased from 1.8 per 10,000 births at 34 weeks to 10.5 per 10,000 births at 42 weeks, whereas the neonatal death risk decreased from 67.7 per 10,000 births at 34 weeks to 26.2 per 10,000 births at 42 weeks, the perinatal mortality risk favored delivery at 39 weeks (RR: 1.17; 99% CI: 1.01–1.36) and not thereafter. In contrast, in the morbidly obese group, stillbirth risk increased from 8.8 per 10,000 births at 34 weeks to 83.7 per 10,000 births at 42 weeks, whereas the neonatal death risk decreased from 63.6 per 10,000 births at 34 weeks to 15.5 per 10,000 births at 42 weeks, the perinatal mortality risk favored delivery from 38 weeks (RR: 1.53; 99% CI: 1.16–2.02) through 41 weeks (RR: 5.39; 99% CI: 1.83–15.88).

Conclusion: The findings reported here suggest that delivery by 38 weeks in gestation minimizes perinatal mortality in pregnancies complicated by maternal morbid obesity.     

Fetal facial expressions in small-for-gestational-age and growth-restricted fetuses

Objective: To evaluate the frequencies of fetal facial expressions among appropriate-for-gestational-age (AGA), small-for-gestational-age (SGA), and growth-restricted (FGR) fetuses.

Methods: Four-dimensional (4D) ultrasound was used to examine the facial expressions of 50 AGA, 25 SGA, and six FGR fetuses between 28 and 35 weeks of gestation. The frequencies of seven facial expressions during 15-minute recordings were assessed. Comparison of facial expressions among the three groups was performed.

Results: Mouthing was the commonest facial expression at 28–35 weeks, and the frequency of mouthing was significantly higher than those of the other six facial expressions in AGA fetuses. Mouthing was the most frequent facial expression, but there was no significant difference in the frequency among mouthing, smiling and blinking in SGA fetuses. Moreover, mouthing displayed a significantly higher frequency than the other facial expressions, except for yawning, smiling, and blinking in FGR fetuses. However, there was no significant difference in the frequency of each facial expression among the three groups.

Conclusions: Our results suggest that the frequencies of fetal facial expressions are not decreased in either SGA or FGR pregnancies. The absence of a decrease in the frequency of each fetal expression in FGR fetuses may be due to increased brain blood flow because of the brain-sparing effect. Moreover, accelerated maturation and development of the brain function, especially the central dopamine system, might be suspected in SGA and FGR fetuses.     

The yield of the prenatal work-up in intrauterine growth restriction and the spectrum of fetal abnormalities detected postnatally†

Objective: To evaluate the yield of work-up in intrauterine growth restriction (IUGR) pregnancies and their outcomes.

Materials and methods: Retrospective data regarding prenatal work-up (serology, genetic testing and imaging), and neonatal outcomes of 198 IUGR pregnancies (estimated fetal weight <10th percentile) were analyzed.

Results: IUGR was isolated in 72 cases. Work-up performed in 158 (80%) cases was positive in 4 (2.5%). No abnormalities were detected in prenatal genetic testing. Echocardiogram performed in 27 cases was abnormal in 3 (11.1%). Serological testing performed in 150 pregnancies (75.8%) detected 1 case (0.7%) of cytomegalovirus (CMV) infection. Thirteen neonates (6.5%) were diagnosed with significant health problems. A positive work-up and significant postnatal health problems were not correlated with IUGR severity, symmetry or additional concurrent findings.

Conclusion: The yield of IUGR work-up is not clear and is probably highest for fetal echocardiography. The rate of significant adverse outcomes after birth is increased in IUGR pregnancies.     

Elevated maternal serum-free β-human chorionic gonadotropin (β-hCG) and reduced risk of spontaneous preterm delivery*

Objective: To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD).

Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded.

Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD.

Conclusions: High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.     

Prevention of unintended pregnancies by using emergency contraception: the differences between levonorgestrel and ulipristal acetate. A theoretical model using data from a survey on the use of emergency contraception in Spain, 2017

Objective: To estimate the differences in unintended pregnancies avoided using either levonorgestrel (LNG) or ulipristal acetate (UPA) emergency contraception (EC).

Design: Cross-sectional study.

Setting: Survey carried out in Spain.

Participants: 1000 Spanish women reporting unprotected sex in 2017.

Main measurements: EC use, reasons for not using EC, calculation of the number of unintended pregnancies avoided.

Results: 39% of Spanish women having had unprotected sex used EC. 61% of those women did not use EC and 11% did not know the existence of this resource. In 2017 the use of EC prevented 101,271 unintended pregnancies. If instead of using LNG every woman had used UPA another 15,979 additional pregnancies could have been prevented.

Conclusions: If all Spanish women having unprotected sex used EC we could expect a significant decrease in the number of unintended pregnancies and abortions. Using UPA instead of LNG would have a greater impact on that reduction with the corresponding benefit for women and society as a whole.     

Correlation between uterine artery Doppler and the sFlt-1/PlGF ratio in different phenotypes of placental dysfunction

Objective: To explore correlations between the sFlt-1/PlGF ratio and uterine arteries (UtA) Doppler indexes in placental dysfunction-related disorders (PDD).

Methods: We prospectively included women with a singleton pregnancy with preeclampsia (PE) only (n = 22), preeclampsia with fetal growth restriction (FGR) (n = 32), FGR only (n = 12), or normal pregnancy (n = 29).

Results: In PDDs, significantly positive correlations between the sFlt-1/PlGF ratio and the mean UtA pulsatility (mPI-UtA), as well as the resistance index (mRI-UtA) were found (p = 0.015, p = 0.019, respectively), but not in normal pregnancies. PDD with signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio and mPI-UtA, was found in 50.0%, and, by the increased sFlt-1/PlGF ratio and mRI-UtA, in 65.2%. PDD without signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio but normal mPI-UtA, was found in 24.2%, and, by the increased sFlt-1/PlGF ratio but normal mRI-UtA, in 7.6%. A substantial proportion of women with signs of impaired placentation were diagnosed with FGR with or without PE.

Conclusion: In PDD, the sFlt-1/PlGF ratio and UtA Doppler indexes increase proportionally. Correlations between the sFlt-1/PlGF ratio and UtA Doppler indexes might help to distinguish between PDDs with and without impaired placentation. However, further studies are needed to explore the correlations in different phenotypes of PDD.     

Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease

Background: The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason.

Materials and methods: We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use.

Results: Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use.

Conclusions: Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother’s cardiac function.     

Computational model for timing of delivery in an obese population

Objective: To estimate the impact on stillbirth risk, cesarean deliveries, and delivery-related healthcare cost associated with induction of labor compared to expectant management of term pregnancies in an obese population.

Methods: A decision analysis model was designed to compare the delivery and cost outcomes associated with a hypothetical cohort of 100,000 term pregnancies, complicated by obesity, that were planning a vaginal delivery. The model predicted stillbirths, cesarean deliveries, and total delivery-related health care cost from routine induction at 39 weeks compared to expectant management and routine induction each week from 40 to 42 weeks.

Results: There were 387 stillbirths avoided by routine induction at 39 weeks compared to the worst-case model of expectant management with induction at 42 weeks. 9234 cesarean deliveries were avoided by routine induction at 39 weeks compared to the worst-case model of expectant management and induction at 41 weeks (30,888 vs. 40,122) . Routine induction at 39 weeks showed a savings in delivery-related health care cost of 30 million dollars compared to the worst-case model of expectant management and induction at 41 weeks (536 million vs. 566 million).

Conclusion: Utilizing this computational model, routine induction at 39 weeks minimizes stillbirths, cesarean deliveries, and delivery-related health care cost.     

Evaluation of the adequacy of Hadlock’s reference chart for identification of fetuses with growth restriction

Objective: This study aimed to verify whether Hadlock’s reference values for fetal weight identify fetuses below the 10th percentile in our population correctly.

Methods: The fitness of the Hadlock reference range to our study population was tested by assessment of Z scores. We evaluated differences between the reference weight ranges proposed in our study and those recommended by Hadlock.

Results: Z scores for Hadlock reference values were non-normally distributed. The difference between the 50th percentile fetal weight proposed by our study model and that proposed by Hadlock was ≤1% at GAs ≥22 weeks and 2–3% at 19–21 weeks. For the 90th percentile level, the maximum difference at GAs ≥17 weeks was 1.5%. For the 10th percentile level, the differences were 2–4% in the third trimester, reaching 8% in week 20 and 13% at a GA of 14 weeks.

Conclusions: The weight reference ranges of this study virtually overlap with the Hadlock ranges. We believe that only at lower gestational ages in the second trimester might some FGR diagnoses be missed in the population study with Hadlock’s reference.     

Non-visualization of fetal gallbladder in microarray era – a retrospective cohort study and review of the literature

Objective: The objective of this study is to examine the frequency of abnormal Chromosomal Microarray (CMA) analyses among fetuses with isolated non-visualization of fetal gallbladder.

Methods: Data from CMA analyses performed due to isolated non-visualization of fetal gallbladder between January 2013 and September 2016 were retrospectively acquired from a computerized database of the Israeli Ministry of Health. The results were compared with the rate for clinically significant CMA findings in general population, based on a large cohort of 5541 pregnancies undergoing CMA due to maternal request, and a systematic review of 9272 cases with normal ultrasound.

Results: Of 45 pregnancies with isolated non-visualization of fetal gallbladder, CMA testing yielded one (2.22%) gain-of-copy-number variant at 16p11.2, categorized as “pathogenic”. In addition, one finding of unknown significance was demonstrated. The risk for clinically meaningful CMA findings among pregnancies with isolated absent gallbladder was not significantly increased compared to control population.

Conclusions: To the best of our knowledge, this study is the first report describing the rate of pathogenic CMA results in fetuses with isolated non-visualization of fetal gallbladder. The results, in conjunction with previous studies, show that the risk for abnormal CMA results in pregnancies diagnosed with non-visualized gallbladder is not significantly different from pregnancies with normal ultrasound.     

Recurrence of extreme serum analytes in consecutive pregnancies and association with obstetrical outcomes*

Objective: To evaluate if presence of extreme maternal serum biochemical analytes recurs in consecutive pregnancies. We hypothesized that presence of >1 extreme analyte in prior pregnancy is associated with increased risk of adverse pregnancy outcome in subsequent pregnancy.

Methods: Retrospective cohort study of singleton pregnancies evaluated and delivered in 2 consecutive pregnancies (2011–2015). Adverse outcomes were defined as indicated preterm delivery before 37 completed weeks due to preeclampsia, fetal growth restriction or other complications.

Results: First and second trimester maternal serum analytes were assessed in 1434 patients in 2 consecutive pregnancies. The presence of >1 extreme serum analyte in prior pregnancy significantly increased likelihood of >1 extreme analyte in subsequent pregnancy. The likelihood increased as number of prior extreme markers increased. In patients with normal outcomes and 2 or more extreme serum analytes in prior pregnancy, there was an increased incidence of adverse pregnancy outcomes in subsequent pregnancy with relative risk (RR) of 5.42 [95% CI 1.6–18.3].

Conclusions: The presence of more than 1 extreme serum marker in one pregnancy increases likelihood of recurrence in subsequent pregnancies. Risk of adverse outcomes in subsequent pregnancy can be evaluated based on biochemistry results as well as prior pregnancy outcomes.     

Listeriosis in two twin pregnancies after in vitro fertilization with differential outcome and literature review

Purpose: In vitro fertilization (IVF) has become a very common procedure in the infertility practice due to its accessibility. The study is aiming at presenting two twin pregnancy-related infections caused by Listeria monocytogenes and reviewing the reported cases of listeriosis in multiple pregnancies.

Materials and methods: Two listeriosis cases with twin pregnancy after IVF were described and the literature on pregnancy-associated listeriosis was reviewed.

Results: The risk of listeriosis should be underscored in pregnant women after IVF, and timely diagnosis and rational treatment might result in a better outcome.

Conclusions: The current study highlights that the infections due to L. monocytogenes should be noted in multiple pregnancies after IVF.     

Early prenatal vitamin D concentrations and social-emotional development in infants

Background: Many pregnant women in the United States have suboptimal vitamin D, but the impact on infant development is unclear. Moreover, no pregnancy-specific vitamin D recommendations have been widely accepted.

Aims: Given the ubiquitous expression of vitamin D receptors in the brain, we investigated the association between early prenatal plasma 25-hydroxyvitamin D (25(OH)D) concentrations and children’s social and emotional development in the Newborn Epigenetic Study, a prospective study of pregnancies from 2009 to 2011 in Durham, North Carolina.

Methods: We measured 25(OH)D concentrations in first or second trimester plasma samples and categorized 25(OH)D concentrations into quartiles. Covariates were derived from maternal questionnaires. Mothers completed the Infant Toddler Social-Emotional Development Assessment when children were 12–24 months of age. We used multivariable linear regression to evaluate associations between 25(OH)D and specific behavior scores, adjusted for season of blood draw, maternal age, education, parity, smoking, marital status, prepregnancy BMI, and infant gender. We investigated effect-measure modification by race/ethnicity.

Results: Of the 218 mother–infant pairs with complete data, Black mothers had much lower 25(OH)D concentrations as compared to White and Hispanic mothers. After adjustment, lower prenatal 25(OH)D was associated with slightly higher (less favorable) Internalizing scores among White children, but lower (more favorable) Internalizing scores among Black and Hispanic children. Lower prenatal 25(OH)D also appears to be associated with higher (less favorable) dysregulation scores, though only among White and Hispanic children.

Conclusions: Though imprecise, preliminary results warrant further investigation regarding a role for prenatal vitamin D on children’s early social and emotional development.     

A scoping review to determine themes that represent perceptions of self as mother (‘ideal mother’ vs ‘real mother’)

Background: Postnatal depression (PND) is a key cause of maternal morbidity, with current systems of initial recognition in the UK detecting only 50% of cases. In attempts to predict those potentially at risk, this review suggests a novel approach.

Aim: Implementing the concept of ‘ideal mother’ versus ‘real mother’, and asking the woman to compare their ‘ideal self’ against ‘existent self’, the aim of this instrument development review was to determine themes from the literature that relate to women’s perceptions of self as a mother, and from this identification develop questions for inclusion within a proposed new measure entitled the Self-Image as Mother Scale (SIMS).

Method: A scoping review of the literature was carried out to identify themes considered to affect perception of self as mother, and from this identification, evidence-based questions for inclusion in the SIMS were developed.

Findings: Themes identified included (1) marital dissatisfaction, (2) inadequate partner support, (3) lack of family support, (4) socioeconomic status and associated poverty, (5) concern about infant, (6) antenatal/postnatal complications, (7) acceptance of infant gender, (8) history of mental health problems, (9) unplanned pregnancy.

Conclusions: From this scoping review 18 questions were developed for inclusion in the SIMS, which will then be evaluated for psychometric properties, scale refinement and validation.     

Correlation between umbilical arterial pH values and fetal vertebral artery Doppler waveforms at the beginning of the second stage of labor: a pilot prospective study

Objective: The aim of this study was to evaluate the association between umbilical arterial pH and fetal vertebral artery Doppler velocimetry waveforms measured at the beginning of the second stage of labor in physiological term pregnancies.

Methods: This was a prospective cohort study of 250 pregnancies. The resistance index, pulsatility index, and peak systolic velocity were measured. The relationship between the fetal Doppler and the umbilical arterial pH was evaluated. A simple linear regression and a general linear model were used to explore possible correlations of Doppler parameters with fetal and neonatal outcome adjusted for confundents.

Results: Umbilical arterial pH values were directly associated with vertebral artery pulsatility index. Fetuses with lower pulsatility index values were at increased risk of a subsequent diagnosis of pathological fetal heart rate tracing patterns (presence of decelerations or reduced variability according to FIGO criteria during the second stage of labor). We estimated a decrease in pulsatility index of 10% in those fetuses destined to show a pathological fetal heart rate tracing.

Conclusion: Vertebral artery Doppler waveforms correlates with umbilical pH in normal pregnancies and is also a function of fetal heart rate patterns. If this proportional association would be demonstrated also for abnormal pH values, vertebral artery pulsatility index might be useful to evaluate fetal wellbeing in those cases of suspected hypoxia/academia.     

Association of first-trimester maternal lipid profiles and triglyceride-glucose index with the risk of gestational diabetes mellitus and large for gestational age newborn

Objective: To evaluate the association of maternal first-trimester plasma lipid profiles, fasting plasma glucose (FPG), and triglyceride (TyG) index with the risk of gestational diabetes mellitus (GDM) and large for gestational age (LGA) infant in Iranian mothers.

Methods: Nine hundred and fifty-four healthy pregnant women were prospectively followed till after delivery. Maternal fasting lipids and glucose concentration were measured at nine-week gestation on average. We used generalized linear models to calculate the relative risks and 95% confidence intervals.

Results: The incidence of GDM and LGA infants among our participants was 18.4% and 26.1%, respectively. There was a significant correlation between the increase in FPG, triglyceride, TG/HDL-C ratio, as well as TyG index with the risk of GDM and LGA infant. After adjusting for potential confounders, the relative risk of GDM in women in the top tertile of FPG, triglyceride (TG), triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) and TyG index was 4.2-, 4.2-, 3.9-, and 4.9-folds of its risk in women in the bottom tertile, respectively. Also after adjusting for GDM, the relative risk of LGA infants in women in the top tertile of FPG, TG, TG/HDL-C ratio and TyG index was 3.9-, 4.3-, 4.8-, and 5.3-folds of its risk in women in the bottom tertile, respectively.

Conclusions: Based on our findings, TyG index is more robust early predictors of GDM and LGA in Iranian women.     

Prospective longitudinal assessment of the fetal left modified Myocardial Performance Index

Introduction: The fetal left modified Myocardial Performance Index (Mod-myocardial performance index (MPI)) is a measure of systolic versus diastolic time intervals obtained from a single cardiac cycle with ultrasound. It is a measure of global ventricular function and has been investigated for potential utility in fetal conditions associated with cardiac dysfunction.

Objectives: The objective of this study is to compare values from a precisely replicated fetal left Mod-MPI technique to published reference ranges.

Methods: Three hundred and sixty-five nulliparae prospectively underwent fetal left Mod-MPI measurement at 27⁺⁰–29⁺⁰ and 35⁺⁰–37⁺⁰ weeks’ gestation. Measurements from pregnancies complicated by gestational diabetes mellitus, preeclampsia, or a small-for-gestational-age (<10th centile) infant were excluded. Mod-MPI values were compared with three published references created using similar measurement techniques.

Results: Compared with one selected reference, at 29⁺⁰ and 35⁺⁰–37⁺⁰ weeks’ gestation, 90–100% of our values fell within the 5th–95th percentile range as expected. Thus, this reference range was validated for our population in late pregnancy. However, the expected level of concordance was not seen at 27⁺⁰–28⁺⁶ weeks’. The other two references to which we compared our Mod-MPI values demonstrated poor concordance, especially at 27⁺⁰–29⁺⁰ weeks’. Pearson interobserver correlation was also improved at 35⁺⁰–37⁺⁰ weeks’ at 0.434, compared with 0.083 at 27⁺⁰–29⁺⁰ weeks’ gestation.

Conclusions: Concordance and interobserver variability between our cohort and similar populations were both improved at 35⁺⁰–37⁺⁰ weeks’ compared with 27⁺⁰–29⁺⁰ weeks’ gestation. Overall, variable Mod-MPI reproducibility across gestations limits clinical application, especially earlier in pregnancy. Manual Mod-MPI measurement should be considered most reliable in late pregnancy until automated MPI measurement is possible.     

Cesarean section in the absence of labor and risk of respiratory complications in newborns: a case-control study

Aim: To establish if labor and gestational age have an additive effect on the likelihood of newborn respiratory complications.

Methods: Case-control study on singleton pregnancies, delivered between 34 and 41 weeks. Cases were collected among newborns discharged with diagnoses of respiratory complications, as codified by ICD 9 1997. Subsequently, pneumonias, meconium aspiration syndromes, and pulmonary hemorrhage were excluded. Controls were all other newborns without respiratory complications. Multivariate analyses were performed hypothesizing and not hypothesizing a relationship between gestational age, labor and newborn adverse respiratory outcomes.

Results: Twenty thousand three hundred and ninety-seven living babies born at term or near-term between January 2006 and December 2010 were assessed. 16,084 infants were included in the analyses. 304 experienced a respiratory complication (cases group). Delivering by cesarean not in labor increases the odds ratio of adverse respiratory outcome by about 2, independently from other variables, among which is gestational age. The same increase of odds ratio of 2 is constantly observed at each week of gestation, from 35 to 39 gestational weeks.

Conclusions: Cesarean not in labor adds a constant risk of newborn respiratory complications at any gestational age near-term and early-term. The more the planned cesarean is delayed, the better is newborn respiratory outcome.     

Major liver resection in pregnancy: three cases with different etiologies and review of the literature

Background: Major liver resection during pregnancy is extremely rare. When required, the associated physiologic and anatomic changes pose specific challenges and greater risk for both mother and fetus

Materials and methods: Three cases of major liver resection during pregnancy due to different etiologies are presented. The relevant literature is reviewed and discussed.

Results: We present three cases of major liver resection due to giant liver hemangioma with Kasabach–Merrit syndrome, giant hydatid cyst, and intrahepatic cholangiocarcinoma, at gestational week (GW) 17, 19, and 30, respectively. All patients had an uneventful postoperative course, continued the pregnancy and gave birth at GW 38.

Conclusion: Major liver resection can be performed safely during pregnancy. A multidisciplinary team of surgeons, anesthesiologists and gynecologists, in a highly experienced tertiary hepatobiliary center, should be involved.