Volume 44, Issue 3 - Highlight: Maternal Medicine

Each year approximately 2400 pregnancies develop folic acid-preventable spina bifida and anencephaly in Europe. Currently, 70% of all affected pregnancies are terminated after prenatal diagnosis. The prevalence of neural tube defects (NTDs) has been significantly lowered in more than 70 countries worldwide by applying fortification with folic acid. Periconceptional supplementation of folic acid also reduces the risk of congenital heart diseases, preterm birth, low birth weight, and health problems associated with child mortality and morbidity. All European governments failed to issue folic acid fortification of centrally processed and widely eaten foods in order to prevent NTDs and other unwanted birth outcomes. The estimated average dietary intake of folate in Germany is 200 μg dietary folate equivalents (DFE)/day. More than half of German women of reproductive age do not consume sufficient dietary folate to achieve optimal serum or red blood cell folate concentrations (>18 or 1000 nmol/L, respectively) necessary to prevent spina bifida and anencephaly. To date, targeted supplementation is recommended in Europe, but this approach failed to reduce the rate of NTDs during the last 10 years. Public health centers for prenatal care and fortification with folic acid in Europe are urgently needed. Only such an action will sufficiently improve folate status, prevent at least 50% of the NTD cases, reduce child mortality and morbidity, and alleviate other health problems associated with low folate such as anemia.

Aim: Our aim was to investigate serum clusterin levels in preeclampsia and to determine whether any changes in clusterin levels are useful in distinguishing the presence of concomitant intrauterine growth restriction (IUGR) and in predicting adverse pregnancy outcomes. Methods: A prospective case-control study was carried out which included 86 pregnant women (47 patients with preeclampsia and 39 healthy controls). Maternal serum samples obtained from all participants and clusterin levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Compared with controls, women with preeclampsia had significantly higher clusterin levels (mean 83.8±23.6 vs. 119.2±40.5, P<0.01). Further analysis revealed the highest clusterin levels were in patients with preeclampsia and IUGR (P<0.001). According to the receiver operating characteristic (ROC) analysis performed for the predictive value of clusterin levels for adverse maternal outcomes, the area under the curve (AUC) was 0.738 (95% CI: 0.616–0.859). The best clusterin cut-off value in predicting adverse maternal outcomes was 102.6 pg/mL with 75% sensitivity and 66% specifity. Multivariable logistic regression analysis revealed serum clusterin levels of >102.6 pg/mL was independently associated with preeclampsia (OR: 6.18, 95% CI: 2.41–15.9) and maternal adverse outcomes (OR: 5.13, 95% CI: 2.01–13.1) and also clusterin levels higher than 117.4 pg/mL were associated with adverse neonatal outcomes (OR: 5.02, 95% CI: 1.04–24.3). Conclusions: The current study suggests that increased levels of clusterin is associated with IUGR and probably predictive for adverse pregnancy outcomes in preeclampsia.

Objective: Preeclampsia is the 2 nd leading cause of maternal mortality in the United States. Women with new-onset or worsening hypertension are commonly evaluated for laboratory abnormalities. We aim to investigate whether demographic and/or clinical findings correlate with abnormal laboratory values. Study design: A retrospective chart review of women who presented for evaluation of hypertension in pregnancy during 2010. Demographic information, medical history, symptoms, vital signs, and laboratory results were collected. Bivariate analysis was used to investigate associations between predictors and the outcome. Result: Of the 481 women in the sample, 22 were identified as having abnormal laboratory test results (4.6%). Women who reported right upper quadrant pain or tenderness had significantly increased likelihood of having laboratory abnormalities compared to those without the complaint. Conclusion: Only a small percentage of women evaluated were determined to have abnormal laboratory findings, predominantly among women with severe preeclampsia. Right upper quadrant pain or tenderness was positively correlated with laboratory abnormalities. The restriction of laboratory analysis in women with clinical evidence of severe disease may be warranted – a broader study should, however, first be used to confirm our findings.

Objective: The aim of this study was to investigate the levels of different isoforms of soluble human leukocyte antigen-G (sHLA-G) in maternal plasma during early and late pregnancy, and to investigate the expression of sHLA-G isoforms in women with early or late-onset severe preeclampsia. Methods: This prospective, nested, case-control study was performed in 24 early-onset severe preeclamptic, 34 late-onset severe preeclamptic, and 74 uncomplicated pregnant women. Plasma levels of sHLA-G1/5 were measured using ELISA. Results: Plasma sHLA-G1 levels in women with late-onset severe preeclampsia were markedly lower compared with normal controls (median: 0 vs. 1.22 ng/mL) at the first trimester, and plasma sHLA-G1 levels in women with early-onset severe preeclampsia were markedly lower compared with normal controls at the second (median: 0 vs. 1.24 ng/mL) and third (median: 0 vs. 1.34 ng/mL) trimesters. There was no difference between the late-onset and early-onset groups at three trimesters. As for sHLA-G5, there was no difference in concentrations among the three groups at any time point. However, compared with controls, more women with early- or late-onset severe preeclampsia had undetectable sHLA-G5 levels in the first (71.4% and 76.2% vs. 14.1%), second (75.0% and 73.3% vs. 19.0%), and third (100.0% and 70.4% vs. 14.8%, respectively) trimester (all P<0.05). sHLA-G1 levels in the first (odds ratio [OR]=0.254, 95% confidence interval [CI]=0.109–0.591, P=0.010), second (OR=0.315, 95% CI=0.158–0.627, P=0.001), and third (OR=0.170, 95% CI=0.054–0.533, P=0.002) trimester was a risk factor for severe preeclampsia. Conclusion: Severe preeclampsia was associated with low/undetectable maternal plasma levels of sHLA-G. Low sHLA-G1 levels might be a risk marker for severe preeclampsia.

Background: Higher 1 st trimester maternal serum levels of interferon-induced protein 10 (IP-10) and interferon inducible T-cell alpha chemoattractant (ITAC) are reported in gestations complicated with preeclampsia. However, parallel results in the fetal circulation are lacking. Objective: To compare IP-10 and ITAC levels in neonatal cord blood from gestations complicated by severe preeclampsia vs. gestational age-matched controls. Method: Umbilical cord vessels were sampled following delivery of women with severe preeclampsia (n=30) ≥36 weeks to measure plasma IP-10 and ITAC levels and compared to corresponding controls matched for parity as well as maternal and gestational age. Chemokines were measured by specific ELISAs and expressed as pg/mL. Rho Spearman’s coefficients were calculated to establish correlations between chemokine values and various numeric variables. Results: Preeclamptic cases displayed significantly lower median plasma umbilical artery and vein levels of both chemokines when compared to controls (IP-10: 23.4 vs. 31.4 and 2.0 vs. 24.6 pg/mL, P<0.05; and ITAC: 2.0 vs. 13.9 and 11.9 vs. 31.6 pg/mL, P<0.05, in artery and vein, respectively). There was a significant correlation between levels of both chemokines (r 2 =0.616, P=0.0001), but not with other variables. Conclusion: In contrast to elevated 1 st trimester levels of IP-10 previously found in the maternal serum of women who later developed preeclampsia, this study found lower umbilical cord IP-10 and ITAC plasma levels in near-term gestations with established severe preeclampsia.

Aims: This study is designed to evaluate predictive value of first-trimester cystatin C levels for long-term pregnancy complications. Methods: The cross-sectional study population consisted of patients who admitted to outpatient clinic of a Maternity Hospital between September 2013 and December 2014. Among the 203 participants who accepted to participate in the study, 174 subjects who continued antenatal follow-up in the same clinic were included in the final analyses. Cystatin C, blood urea nitrogen, Creatinine levels and estimated glomerular filtration rates were evaluated in the first-trimester routine antenatal visit. Mode of delivery and gestational complications were noted. Results: First-trimester cystatin C levels were significantly higher in cases complicated with preterm delivery and premature rupture of membrane (PROM) compared to uncomplicated ones (0.58±0.07 vs. 0.55±0.07, P=0.041, and 0.58±0.07 vs. 0.55±0.07, P=0.036). With a cutoff value of 0.505 mg/L, sensitivity of cystatin C for preterm delivery and PROM was 91.9% and specificity was 27.7% with a negative predictive value of 92.3% and a positive predictive value of 26.6%. Conclusion: Detection of cystatin C levels in the first trimester of pregnancy for the prediction of preterm/PROM seems as a promising preliminary data. The relatively higher first-trimester cystatin C levels in complicated pregnancies are conspicuous. The results imply that in pregnancy cystatin C might be more than a marker for renal function.

Objective: The objective of this study was to monitor the maternal mortality ratio (MMR) in 19 general hospitals after introducing quality assurance in four states in Nigeria. Methods: Data collection with a structured maternity record book started in 2008 in ten rural hospitals in Kano and Kaduna State. In 2011, five hospitals from Federal Capital Territory Abuja were added, whilst in 2013 four hospitals were added from Ondo State. The routine data collection was conducted by experienced midwives and supervised by obstetricians from each of the states. However, the data from all four states were collated centrally at Aminu Kano Teaching Hospital for analysis. Results: From 2008 to 2013, 121,808 deliveries were evaluated; MMR fell from 1380 to 360/100,000 in Kaduna State, whilst for Kano State there was a gradual reduction of MMR from 2100/100,000 in 2008 to 1070/100,000 in 2011, and then it increased to 2150/100,000 in 2013. Ondo state had the lowest MMR of 180/100,000 in 2013 followed by Abuja with 240/100,000. The median cesarean section rate was 8.19%, (range 0.97–22.53%), eclampsia/preeclampsia was 4.43% (range 0–56.55%), and postpartum hemorrhage was 3.36% (range 0.81–11.4%). Conclusions: Quality assurance in rural hospitals generates the awareness necessary to improve maternal health and lead to reduction of MMR.

The conditions of iron deficiency are highly incident in pregnancy with elevated risks for preterm birth and low birth weight. In our recent study, we found 6% of participants having anemia, whereas between 39% and 47% showed iron deficiency without anemia. In many countries in prenatal care solely hemoglobin (Hb) measurement is applied. For the gynecologists till date there is no indication to determine other markers (e.g., serum-ferritin). As iron deficiency results from an imbalance between intake and loss of iron, our aim was to find out if the risk of iron deficiency conditions can be estimated by a diet history protocol as well as questionnaires to find about iron loss. We found that the risk of having iron deficiency in upper gestational week (>=21) increased by a factor of five. Thus, additional diagnostics should be done in this group by now. Using the questionnaire as a screening instrument, we further estimated the probability of disease in terms of a positive likelihood ratio (LR+). The positive LR for the group below 21 th week of gestation is 1.9 thus, increasing the post-test probability to 52% from 36% as before. Further research based on higher sample sizes will show if the ratios can be increased further.

Aim: The aim of this study was to evaluate the relationship between serum sirtuin-1 (SIRT1) level and neutrophil-lymphocyte ratio (NLR) with hyperemesis gravidarum (HG). Methods: Overall, 90 patients who presented with pregnancy between August 2013 and November 2014 were included in the study. The patients were divided into two groups: patients with HG (n=45) and patients without HG (control group [C]; n=45). The patients with comorbid conditions other than pregnancy (disease or medication) were excluded. In all patients, demographic data including age, body mass index (BMI), gestational week, and smoking status were recorded. Blood samples were drawn for complete blood count and measurements of blood lipid, liver enzymes, serum SIRT1, and insulin levels. NLR was calculated from CBC. Results: No significant differences were detected in age, BMI, or GA between groups (P>0.05). Serum SIRT1 and NLR were found to be significantly higher in patients with HG compared with those in the control group (P=0.001 and 0.006, respectively). Conclusion: In HG, both SIRT1 level and NLR increased. In HG, this occurred as a response to metabolic alterations and potential inflammation.

Aim: The purpose of our study is to compare pregnancy outcomes between women with a functioning renal transplant and women with end-stage renal disease (ESRD). Methods: We carried out a population-based retrospective cohort study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database from 2006 to 2011. Logistic regression analysis was used to estimate the age-adjusted effect of functioning renal transplant vs. ESRD requiring dialysis on pregnancy outcomes. Results: We identified 264 birth records to women with a functional renal transplant and 267 birth records to women with ESRD on dialysis among 5,245,452 births. As compared to women with ESRD on dialysis, renal transplant recipients were less likely to have placental abruption [odds ratio, OR 0.23 (95% confidence interval, CI 0.08–0.70)], to receive blood transfusions [OR 0.17 (95% CI 0.09–0.30)], and to have growth-restricted and small-for-gestational-age babies [OR 0.45 (95% CI 0.23–0.85)]. Renal transplant recipients were more likely to have an instrumental delivery [OR 15.38 (95% CI 1.92–123.3)]. Among renal transplant women, there was a trend towards delivery by cesarean section as compared to patients with ESRD [OR 1.31 (95% CI 0.93–1.85)]. However, these results were not statistically significant. Fetal deaths were less likely to occur in women with a renal transplant [OR 0.41 (95% CI 0.17–0.96)]. There were four maternal deaths among patients with ESRD on dialysis and no maternal deaths among renal transplant patients. Conclusion: Patients with a functional renal graft had an overall lower rate of morbidity and adverse pregnancy complications when compared to patients with ESRD on dialysis.

Objective : Motor vehicle accidents (MVAs) are a major incidental cause of pregnancy-associated maternal deaths in the US. The goal of this research was to evaluate the incidence, risks, and fetal and maternal outcomes of pregnant women involved in MVAs. In addition, we examined the relationship between the injury severity score (ISS) and car seat location in pregnant and non-pregnant women. Methods : This involved a retrospective cohort study of female patients who were involved in MVAs and hospitalized between the years 2006 and 2013. Data were collected from the Israeli National Trauma Registry. Severity and outcomes of pregnant and non-pregnant women with blunt trauma were compared. Results : In this study, 3794 pregnant and 3441 non-pregnant patients aged 18–40 years were analyzed. The majority of pregnant patients were drivers (n=2515, 67%) as opposed to passengers (n=1279, 33%). Pregnant patients had lower ISS than non-pregnant patients (P<0.001). Out of these pregnant patients, 38 (1%) had adverse maternal-fetal pregnancy outcomes, including (1) placental abruption 0.1% and (2) miscarriage (0.2%). One pregnant patient died (0.03%) compared with 32 (0.93%) of the non-pregnant patients (P<0.0001). A significant negative correlation between gestational age and spontaneous abortion was found (P<0.009). Conclusions: The severity of injury and the mortality rate of pregnant patients involved in MVAs are significantly lower compared with non-pregnant patients. Pregnant drivers had a significantly lower severity of trauma compared with pregnant passengers.

Amniotic fluid cells (AFC) from 2 nd trimester amniocentesis have been found to be a source of multipotent stem cells which might overcome the limitations of expansion, histocompatibility, tumorigenesis, and ethical issues associated with using human embryonic cells, umbilical cord, cord blood, bone marrow, and induced pluripotent cells. Previous work by our group and others demonstrated multipotency and the ability to grow well in culture. However, all these studies were done in media containing fetal calf serum. We sought to observe the properties of AFC grown in serum-free media as that would be required for clinical transplantation in humans. Fresh samples were obtained from three patients, and each sample divided into a culture whose cells were not exposed to fetal calf serum, and the other half into a standard culture medium containing fetal calf serum. Doubling time and stem cell marker expression by flow cytometry were assessed. Differentiation to neural, osteoid, and chondrogenic lineages was induced using appropriate media and confirmed by fluorescent microscopy, histology, and immunohistochemistry. There were no statistically significant differences between cells grown serum-free and in standard media in any of these parameters. The data supports the possibility of clinical use of AFC in stem cell transplantation.

Objectives: This study aimed to evaluate antenatal risk factors associated with symptomatic congenital cytomegalovirus (CMV) disease, following in utero vertical infection. Methods: This study included a retrospective cohort of 155 neonates with congenital CMV infection, following primary maternal CMV infection during pregnancy, and were divided to symptomatic (n=95) and asymptomatic (n=60) newborns. Results: Young maternal age (29.1±5.12 vs. 31.6±5.36 years, P=0.005), high risk occupation for viral exposure (20.0% vs. 11.7%, P=0.04), CMV IgG seroconversion at diagnosis (83.1% vs. 63.3%, P=0.005) and abnormal fetal MRI (11.6% vs. 0%, P=0.003) were found to be prognostic risk factors associated with symptomatic CMV disease of the newborn. Maternal febrile illness at diagnosis, IgG avidity, US findings and the timing of maternal infection were not associated with the occurrence of neonatal symptoms. Conclusions: Knowledge of the reported risk factors may assist in counseling parents with intra uterine CMV infection.

Objective: Preeclampsia leads to chronic intrauterine hypoxia by interfering with placental blood supply. The aim of this study was to investigate whether preeclampsia exposure has an influence on the central nervous system of infants, as monitored by amplitude integrated electroencephalography (aEEG). Methods: We recruited 52 infants with gestational age between 30 and 34 weeks. Twenty-seven infants were born to preeclamptic mothers, and 25 gestational age-matched infants whose mothers were healthy were enrolled as a control group. aEEG recordings were performed between 24 and 48 h of life using a cerebral function monitor (CFM) (Olympic Brainz monitor). Along with aEEG, middle cerebral artery (MCA) blood flow velocities (BFV) were measured using Doppler ultrasound. Results: The duration of quiet sleep was significantly shorter (P=0.001), and Burdjalov score was lower (P=0.04) in the preeclampsia group. However, there was no change in MCA BFV in this group. Conclusions: Preeclampsia altered cerebral electrical activity of premature infants born to preeclamptic mothers.

Our purpose was to investigate the influence of a uterine curettage on the immediate maternal sFlt-1 concentration post partum. Forty-six patients booked for delivery via primary caesarean section were included in a prospective open, case control study. Eighteen of them achieved an intraoperative curettage and formed the treatment group, 28 patients without curettage were enrolled in the control group. Maternal sFlt-1 serum values were measured immediately before and 24 h after delivery. Patients who underwent a uterine curettage showed a relative decrease of 70% (median 3670±1110 pg/mL–1143±270 pg/mL) in comparison to the control group with 65% (median 3132±636 pg/mL–1098±611 pg/mL; P=0.558). Additionally, three patients with preeclampsia and curettage were included, who showed a relative decrease of 76%. A uterine curettage may slightly accelerate the fall of the postpartal sFlt-1 concentration. The previously described benefit of curettage in patients with preeclampsia regarding faster recovery or treatment of postpartum seizures may be partly explained as mediated by anti-angiogenic factors.