Volume 47, Issue 7

Background Altered cardiac geometry affects a proportion of fetuses with growth restriction (FGR). The aim of this study was to explore the hemodynamic factors associated with cardiac remodeling in late FGR. Methods This was a prospective study of singleton pregnancies complicated by late-onset FGR undergoing assessment of left (LV) and right (RV) ventricular sphericity-index (SI). The study population was divided in two groups according to the presence of cardiac remodelling, defined as LVSI <5 th centile. The following outcomes were explored: gestational age at birth, birthweight, caesarean section (CS) for fetal distress, umbilical artery (UA) pH and neonatal admission to special care unit. The differences between the 2 groups in UA pulsatility index (PI), middle cerebral artery (MCA) PI, uterine artery PI, cerebroplacental ratio (CPR) and umbilical vein (UV) flow corrected for fetal abdominal circumference (UVBF/AC) were tested. Results In total, 212 pregnancies with late FGR were enrolled in the study. An abnormal LV SI was detected in 119 fetuses (56.1%). Late FGR fetuses with cardiac remodeling had a lower birthweight (2390 g vs. 2490; P = 0.04) and umbilical artery pH (7.21 vs. 7.24; P = 0.04) and were more likely to have emergency CS (42.8% vs. 26.9%; P = 0.023) and admission to special care unit (13.4% vs. 4.3%; P = 0.03) compared to those with normal LVSI. No difference in either UA PI (p = 0.904), MCA PI (P = 0.575), CPR (P = 0.607) and mean uterine artery PI (P = 0.756) were present between fetuses with or without an abnormal LV SI. Conversely, UVBF/AC z-score was lower (−1.84 vs. −0.99; P ≤ 0.001) in fetuses with cardiac remodeling and correlated with LV (P ≤ 0.01) and RV SI (P ≤ 0.02). Conclusion Fetal cardiac remodelling occurs in a significant proportion of pregnancies complicated by late FGR and is affected by a high burden of short-term perinatal compromise. The occurrence of LV SI is independent from fetal arterial Dopplers while it is positively associated with umbilical vein blood flow.

Background Although pregnancy is frequently associated with mental states of happiness, hope and well-being, some physical and psychological changes can contribute to increased sleep disturbances and worsened sleep quality. Sleep quality has been linked to negative emotions, anxiety and depression. The main objective of this paper was to systematically review the impact of sleep during pregnancy on maternal mood, studying the association between objective and subjective measures of sleep quality and perinatal depression. Methods We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, which included studies published between January 2008 and April 2019, and met the following criteria: (i) studies on pregnant women assessing the effects of sleep quality variables on perinatal mood disorders, (ii) studies published in English and (iii) full paper published in a peer-reviewed scientific journal with full-text format available. Results A total of 36 studies published in the last decade met the inclusion criteria for qualitative review and eight of them were suitable for meta-analysis. Both confirmed the negative effects of poor sleep on perinatal mood. However, qualitative analysis showed that unrepresentative samples and low participation rates falling below 80% biased some of the studies. The standard random-effects meta-analysis showed a pooled size effect [ln odds ratio (OR) 1.49 (95% confidence interval [CI] 1.19, 1.79)] for perinatal depression in cases of poor prenatal sleep quality, although heterogeneity was moderate to high [Q 16.05, P ≤ 0.025, H 2 2.45 (95% CI 1.01, 13.70)]. Conclusion Poor sleep quality was associated with perinatal mood disturbances. The assessment of sleep quality along the pregnancy could be advisable with a view to offering preventative or therapeutic interventions when necessary.

Background Spontaneous miscarriages are common pregnancy complications which result in psychological and emotional burden in the affected women. It is therefore necessary to identify biomarkers that can predict pregnancy outcome in women with threatened miscarriages so as to assist in their counselling and management. Methods The study compared levels of maternal serum CA125 in 65 pregnancies with threatened miscarriages (study group) with 65 normal intrauterine pregnancies (control group) between 6 weeks and 19 weeks + 6 days gestation using an enzyme linked immunosorbent assay (ELISA) technique. Results The mean age of the study and control groups were 29.5 ± 0.14 years and 30.1 ± 0.14 years, respectively. The mean serum CA125 in the study group was 30.1 ± 1.1 IU/mL while that of the control group was 22.9 ± 1.2 IU/mL and this was statistically significant (P = 0.0001). The mean serum CA125 level in the women whose pregnancies were aborted (aborters) was 34.8 ± 1.4 IU/mL while the mean value among those whose pregnancies continued till term (non-aborters) was 27.3 ± 1.2 IU/mL. This was statistically significant (P = 0.001). Further analysis using CA125 ≥36.2 IU/mL (mean value of serum CA125 among aborters + 1 standard deviation) as a threshold for intrauterine pregnancies that eventually got aborted showed a sensitivity of 66.7%, specificity of 83.3%, positive predictive value of 55.6%, negative predictive value of 88.9% and the diagnostic effectiveness (accuracy) was 79.4%. Conclusion The measurement of serum CA125 is a useful predictor of pregnancy outcome in threatened miscarriages.

Background Thyroid cancer is one of the most common cancers in women of reproductive age. Our purpose was to evaluate the association between thyroid cancer and maternal and neonatal outcomes of pregnancy. Methods We conducted a retrospective cohort study using the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) database from the US. A cohort consisting of women who delivered between 1999 and 2014 was created. Multivariate logistic regression, controlling for baseline maternal characteristics, was used to compare pregnancy complications and neonatal outcomes of pregnant women with thyroid cancer [International Classification of Diseases, ninth edition (ICD-9) code 193] diagnosed before or during pregnancy with those of the obstetric population without thyroid cancer. Results The study included 14,513,587 pregnant women, of which 581 women had a diagnosis of thyroid cancer (4/100,000). During the observation period, there was an upward trend in the prevalence of thyroid cancer among pregnant women, though not statistically significant (P = 0.147). Women with thyroid cancer were more likely to be Caucasian, belong to a higher income quartile, have private insurance, to be discharged from an urban teaching hospital and to have pre-gestational hypertension. Women with thyroid cancer had a greater chance of delivering vaginally, requiring transfusion of blood and developing venous thromboembolism (VTE). Neonates of mothers with thyroid cancer were not found to be at increased risk for the adverse neonatal outcomes examined, specifically, congenital malformations, intrauterine growth restriction, fetal death and preterm labor. Conclusion Pregnancies complicated by thyroid cancer have higher incidences of VTE and need for transfusions, with comparable overall newborn outcomes.

Background We aimed to analyze the success rate of external cephalic version (ECV) for breech presentations performed in our center between March 2011 and March 2016. We evaluated factors related to a successful ECV, delivery mode, complications and newborn status after ECV. Methods Analysis of assembled data of 327 consecutive ECVs in the third trimester was done. Results The total success rate was 56.6%. After a successful ECV, 85.9% of the fetuses were delivered vaginally. Logistic regression analysis of background factors leading to a successful ECV showed that tocolysis with ritodrine and anterior placenta were each significantly correlated with the rate of successful version. No severe complications were registered during the ECVs, and all babies had normal Apgar scores at delivery. Conclusion These findings suggest that attempting an ECV in breech presentations, once or even twice, seems to be an appropriate management given that a successful ECV decreases the rate of cesarean section in this group of patients and by doing so, it might also decrease the risk of cesarean sections in future pregnancies.

Background Pregnancy is associated with biochemical changes leading to increased nutritional demands for the developing fetus that result in altered micronutrient status. The Indian dietary pattern is highly diversified and the data about dietary intake patterns, blood micronutrient profiles and their relation to low birthweight (LBW) is scarce. Methods Healthy pregnant women (HPW) were enrolled and followed-up to their assess dietary intake of nutrients, micronutrient profiles and birthweight using a dietary recall method, serum analysis and infant weight measurements, respectively. Results At enrolment, more than 90% of HPW had a dietary intake below the recommended dietary allowance (RDA). A significant change in the dietary intake pattern of energy, protein, fat, vitamin A and vitamin C (P < 0.001) was seen except for iron (Fe) [chi-squared (χ 2 ) = 3.16, P = 0.177]. Zinc (Zn) deficiency, magnesium deficiency (MgDef) and anemia ranged between 54–67%, 18–43% and 33–93% which was aggravated at each follow-up visit (P ≤ 0.05). MgDef was significantly associated with LBW [odds ratio (OR): 4.21; P = 0.01] and the risk exacerbate with the persistence of deficiency along with gestation (OR: 7.34; P = 0.04). Pre-delivery (OR: 0.57; P = 0.04) and postpartum (OR: 0.37; P = 0.05) anemia, and a vitamin A-deficient diet (OR: 3.78; P = 0.04) were significantly associated with LBW. LBW risk was much higher in women consuming a vitamin A-deficient diet throughout gestation compared to vitamin A-sufficient dietary intake (OR: 10.00; P = 0.05). Conclusion The studied population had a dietary intake well below the RDA. MgDef, anemia and a vitamin A-deficient diet were found to be associated with an increased likelihood of LBW. Nutrient enrichment strategies should be used to combat prevalent micronutrient deficiencies and LBW.

Background Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are used as markers of preeclampsia. The aim of this paper was to assess the correlations between the sFlt-1/PlGF ratio values within the <38, 38–85 and >85 brackets and perinatal outcomes in pregnancies that require determination of these markers. Methods A total of 927 pregnant patients between 18 and 41 weeks’ gestation suspected of or confirmed with any form of placental insufficiency (preeclampsia, intrauterine growth restriction [IUGR], gestational hypertension, HELLP syndrome, placental abruption) were included in the study. In each of the patients, the sFlt-1/PlGF ratio was calculated. Patients were divided into three groups according to the sFlt-1/PlGF ratio brackets of <38, 38–85 and >85. Results Significantly worse perinatal outcomes were found in the sFlt-1/PlGF >85 group, primarily with lower cord blood pH, neonatal birth weight and shorter duration of gestation. Statistically significant correlations between the values of these markers and the abovementioned perinatal effects were found. Conclusion An sFlt-1/PlGF ratio value of >85 suggests that either preeclampsia or one of the other placental insufficiency forms may occur, which is associated with lower cord blood pH, newborn weight and earlier delivery. Determining the disordered angiogenesis markers and calculating the sFlt-1/PlGF ratio in pregnancies complicated by placental insufficiency may lead to better diagnosis, therapeutic decisions and better perinatal outcomes.

Background Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta. Methods Placental explant cultures were treated with BPA (0–10,000 nM) in the presence or absence of 10 7 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA). Results Under basal conditions, IL-1β and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000–10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1β, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production. Conclusion BPA may increase placental inflammation by promoting IL-1β and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.

Objective To compare the efficacy of misoprostol vaginal insert (MVI) for labor induction using standard and adjusted criteria. Methods A single-center, comparative cohort study using a consecutive series of pregnant women ≥37/0 weeks undergoing labor induction with either standard criteria for MVI (administration for up to 24 h; MVI-24) or with adjusted criteria (MVI administration for a maximum of 10 h; MVI-10) conducted at a tertiary academic center in Germany. The primary outcomes were the time from start of induction to any delivery and cesarean delivery rate. Results A total of 138 women were included in the study, 69 in each group. The mean time from MVI administration to any delivery showed no significant difference between the MVI-24 and MVI-10 groups (954 vs. 969 min, respectively; P = 0.679). The cesarean delivery rate was proportionally lower for the MVI-10 group [39.1% (27/69) vs. 24.6% (17/69); P = 0.10]. Conclusion The time from induction to delivery with MVI was similar when using standard criteria of up to 24 h of exposure vs. adjusted criteria of up to 10 h of exposure. Although the threshold for statistical significance for cesarean section was not attained, there is nonetheless a considerable difference between the MVI-24 and MVI-10 groups.

Objective To construct new reference values for biometrical measurements and sonographic estimated fetal weight (sEFW) in twin gestations and compare them to previously published normograms. Methods A retrospective analysis of sEFW evaluations of twin gestations was performed between 2011 and 2016 in a single university-affiliated medical center. sEFW was calculated using the Hadlock 1985 formula. To avoid selection bias, one evaluation per pregnancy was randomly selected. Following mathematical transformation to obtain normality of values, normograms were constructed using a best-fit regression model for estimation of mean and standard deviation at each gestational age (GA). Normograms were validated by applying all observations to ensure equal distribution at parallel percentiles. Our normograms were then compared to previously published sEFW normograms for twin gestations. Results A total of 864 sEFW evaluations were performed on 195 twin pregnancies at 22–39 gestational weeks. Of them, 390 entered the primary analysis. The rest were left for validation. Seventy percent of the cohort were dichorionic-diamniotic twins (136/195), 16% (32/195) were monochorionic-diamniotic twins and three (1.5%) were monochorionic-monoamniotic twins. Twenty-four fetuses lacked data on chorionicity. The rest were monochorionic twins or were of unknown chorionicity. Values corresponding to the 2.5 th , 10 th , 50 th , 90 th and 97.5 th percentiles for sEFW are presented for every GA. Validation by applying all 864 evaluations on constructed normograms was achieved. Comparison to previously published twins’ sEFW normograms demonstrated wide variation between curves. Conclusion New reference values for biometrical measurements and sEFW in twin gestations are presented for clinical and research use. Comparison to other curves demonstrates the wide variability and need for further investigation on twin’s normal growth.

Background Bisphenol A (BPA) is an estrogenic, endocrine-disrupting compound widely used in the industry. It is also a ubiquitous environmental pollutant. Its presence was confirmed in human fetuses, which results from maternal exposure during pregnancy. The mechanisms behind maternal-fetal transfer, and relationships between pregnant women and fetal exposures remain unclear. The aim of this study was to assess the impact of maternal exposure to BPA on the exposure of the fetus. Methods Maternal plasma and amniotic fluid samples were collected from 52 pregnant women undergoing amniocentesis for prenatal diagnosis of chromosomal abnormalities. BPA was measured by gas chromatography-mass spectrometry (GC-MS). The permeability factor – a ratio of fetal-to-maternal BPA concentration – was used as a measure delineating the transplacental transfer of BPA. Results The median concentration of maternal plasma BPA was 8 times higher than the total BPA concentration in the amniotic fluid (8.69 ng/mL, range: 4.3 ng/mL–55.3 ng/mL vs. median 1.03 ng/mL, range: 0.3 ng/mL–10.1 ng/mL). There was no direct relationship between the levels of BPA in maternal plasma and amniotic fluid levels. The permeability factor, in turn, negatively correlated with fetal development (birth weight) (R = −0.54, P < 0.001). Conclusion Our results suggest that the risk of fetal BPA exposure depends on placental BPA permeability rather than the levels of maternal BPA plasma concentration and support general recommendations to become aware and avoid BPA-containing products.

Background Spina bifida affects 0.5–1 in 1000 pregnancies in the United States and is often diagnosed in the mid-second trimester. The objective of the study was to directly compare ultrasounds (US) and magnetic resonance imaging (MRI) obtained in the antenatal period in the diagnosis and localization of fetal myelomeningocele (MMC) and compare these with the postnatal outcomes of these infants Methods A retrospective analysis of patients referred to the Fetal Care Center at the Cleveland Clinic from 2005 to 2017. US and MRIs were obtained from the Cleveland Clinic electronic medical record. Infants were followed-up at an interdisciplinary myelomeningocele pediatrics clinic. Results MRI and US varied in correlation with physical exam at the time of birth and surgery. While no differences were detected in demographics, pregnancy outcomes or pediatric outcomes, it was noted that the majority of patients developed neurogenic bladders irrespective of the lesion level. Conclusion MRI is not superior to US in the diagnosis of MMC. Pregnancies complicated by MMC do not vary in morbidity, and pediatric outcomes remain similar regardless of the lesion level. This data provides additional information for the counseling of patients when faced with this antenatal diagnosis.

Objective To assess the association between fetal malnutrition (FM) and the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) in singleton term appropriate for gestational age (AGA) neonates. Methods This cross-sectional observational study was performed with 4340 singleton, term AGA neonates without perinatal disease over a two-year period. Results A total of 4320 neonates were evaluated in this study. Those diagnosed with fetal malnutrition, 284 (6%) neonates, were compared with 150 healthy term AGA neonates. Gestational week, birth weight, birth height, head circumference, maternal age, last pregnancy weight, and status of income of the FM group were found to be lower when compared to the control group (P = 0.011). Low last pregnancy weight (P = 0.017) and low level of income (P = 0.042) were found to be factors that affect the presence of FM. The NLR and PLR were found to be significantly higher in the FM group compared with term AGA healthy controls. In correlation analyses, there was a negative correlation between the NLR and PLR with fetal nutritional status (P = 0.011 and P < 0.001, respectively). When the NLR level was taken as 4.51, the sensitivity and specificity of the test for FM were calculated as 81.2% and 80.8%, respectively [area under the receiver-operating characteristic curve (AUROC): 0.81]; when the PLR level was taken as 155.4, the sensitivity and specificity of the test for FM were calculated as 87.0% and 85.4%, respectively (AUROC: 0.94). Conclusion Cord-blood NLR and PLR negatively correlate with term FM AGA neonates.

Background Smoking during pregnancy still exists in daily life but the effect on the newborn in the early stage of life is still unclear. This study investigates the normal reference range of carboxyhemoglobin (HbCO) in umbilical cord blood gas (UBG). Methods A single center retrospective cross-sectional cohort study was performed with 1172 cases. We analyzed HbCO values in umbilical cord blood, maternal smoking, birth weight percentiles, duration of amenorrhea and maternal admission duration prior to delivery. Results HbCO levels in newborns range from 0 to 7.7% with a mean of 0.6% (standard deviation 0.6). Newborns from women who smoked during pregnancy have a significant higher HbCO value compared to newborns from women who did not smoke. Birth weight is negatively correlated with HbCO (P = 0.001). Conclusion Our results show the normal reference range in this study is 0–1.2% for HbCO in the umbilical blood of newborns. Smoking prior to delivery leads to a higher HbCO value in the UBG sample of the newborn, a lower birth weight and may be potential harmful.

Background Human milk is the optimal source of nutrition for preterm infants. However, breast milk alone is often not sufficient to satisfy the high nutritional needs for growth and development in preterm infants. Fortified human breast milk is the best way to meet the nutritional needs of preterm infants. Human breast milk is fortified according to the estimated nutrient content of mature breast milk; however, because the content of breast milk is highly variable, the macronutrient support may be more or less than needed. The goal of this study was to analyze the macronutrient content of preterm human milk during the first 6 weeks of lactation. Methods The study included 32 mothers of preterm infants with a gestational age of ≤32 weeks. Breast milk was collected in 24-h cycles and analyzed daily using mid-infrared (MIR) spectroscopy. We measured protein, fat and lactose concentrations in the breast milk, and the energy content was calculated. Results The protein content was high during the first weeks of lactation, but decreased as lactation progressed. The fat, energy and lactose contents of the breast milk were low during the first 2 weeks of lactation, increased as lactation progressed and remained constant thereafter. In women with high body mass index (BMI), higher protein levels were found in transitional milk. In women who had high income level, higher fat and energy levels were found in transitional milk. Conclusion Our findings indicate that the macronutrient content of preterm breast milk changes throughout the course of lactation, with BMI and income level. Knowledge of the macronutrient composition of breast milk is necessary to ensure that preterm infants receive the appropriate types and quantities of nutrients to promote optimal growth, and to ensure that breast milk is fortified according to individual needs. Our findings may be useful for the provision of optimal nutritional support for preterm infants.