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Natural killer (NK) cells that provide first-line innate immune reactions against virus-infected and tumor cells have different roles in different body sites and in different stages. From the beginning of life, NK cells participate in many aspects of development, especially in a successful pregnancy and a healthy neonatal stage. This article reviews recent advances regarding the role of NK cells in implantation, placentation and immune tolerance during pregnancy as well as in the neonatal immune defense. The interactions between NK cells and other immune cells in each developmental stage are discussed.

Introduction: The objectives of this study were: 1) to determine the amniotic fluid (AF) microbiology of patients with the diagnosis of clinical chorioamnionitis at term using both cultivation and molecular techniques; and 2) to examine the relationship between intra-amniotic inflammation with and without microorganisms and placental lesions consistent with acute AF infection. Methods: The AF samples obtained by transabdominal amniocentesis from 46 women with clinical signs of chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anerobic bacteria as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation [defined as an AF interleukin 6 (IL-6) concentration ≥2.6 ng/mL], and placental lesions consistent with acute AF infection (acute histologic chorioamnionitis and/or acute funisitis) were examined according to the results of AF cultivation and PCR/ESI-MS as well as AF IL-6 concentrations. Results: 1) Culture identified bacteria in AF from 46% (21/46) of the participants, whereas PCR/ESI-MS was positive for microorganisms in 59% (27/46) – combining these two tests, microorganisms were detected in 61% (28/46) of patients with clinical chorioamnionitis at term. Eight patients had discordant test results; one had a positive culture and negative PCR/ESI-MS result, whereas seven patients had positive PCR/ESI-MS results and negative cultures. 2) Ureaplasma urealyticum (n=8) and Gardnerella vaginalis (n=10) were the microorganisms most frequently identified by cultivation and PCR/ESI-MS, respectively. 3) When combining the results of AF culture, PCR/ESI-MS and AF IL-6 concentrations, 15% (7/46) of patients did not have intra-amniotic inflammation or infection, 6.5% (3/46) had only MIAC, 54% (25/46) had microbial-associated intra-amniotic inflammation, and 24% (11/46) had intra-amniotic inflammation without detectable microorganisms. 4) Placental lesions consistent with acute AF infection were significantly more frequent in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [70.8% (17/24) vs. 28.6% (2/7); P=0.04]. Conclusion: Microorganisms in the AF were identified in 61% of patients with clinical chorioamnionitis at term; 54% had microbial-associated intra-amniotic inflammation, whereas 24% had intra-amniotic inflammation without detectable microorganisms.

Background: Differences exist in obstetric intervention rates between hospitals but it is not known if the individual consultant governs the decision to intervene or whether intervention is a product of agreed protocols and working practices. The purpose of this study is to analyse the differences in obstetric intervention rates amongst individual consultants working in a large maternity unit. Methods: Each consultant was responsible for all deliveries occurring in successive 24-h periods. Over a 6-year period all deliveries resulting from a spontaneous onset of labour were matched to the consultant in charge at the time of the delivery and analysed. Results: There were no differences seen in normal delivery rates (χ 2 =4.478, P=0.812) and vacuum (χ 2 =12.232, P=0.141) rates for the consultants. Significant differences were found in both forceps rate (χ 2 =21.462, P=0.006) and caesarean rate (χ 2 =24.535, P=0.002) between consultants. When the forceps rate was combined with vacuum rate there were no significant differences. Conclusions: Within the hospital, individual consultants demonstrated no significant variations in overall intervention rates. However, when intervention occurred, different consultants showed preferences for forceps and caesarean section.

Aims: Recent studies indicate that older women are more likely to consume alcohol during pregnancy, but subgroups at highest risk within the context of maternal age have not been identified. This study identifies subgroups at risk for alcohol use during pregnancy among three age categories using classification and regression trees (CART) analysis. Methods: Using the 2002–2009 Pregnancy Risk Assessment Monitoring System (PRAMS) dataset (311,428 records of U.S. women), logistic regression and classification trees were constructed separately for age groups, ≤24, 25–29, and ≥30 years. Results: Overall, 6.5% of women reported drinking alcohol during the last trimester of pregnancy. Alcohol consumption by age group was: 3.7% for ≤24, 5.7% for 25–29, and 10.1% for ≥30 years of age. Women ≤24 years were at greater risk of consuming alcohol if they also smoked (5.8%). Among nonsmokers, higher levels of education and being Hispanic were associated with a 35% increase in alcohol use. Distinct high-risk subgroups emerged for the 25–29-year-old group. Specifically, 12.8% of non-obese women who reported having experienced abuse during pregnancy also reported drinking alcohol in the last trimester. About 16% of women ≥30 years with at least 16 years of education, White or Hispanic with normal or underweight BMI, drank alcohol during their last trimester. Conclusions: Given limited health care resources for prevention and treatment, the early identification of high-risk groups for prenatal alcohol use is critical. This study provides evidence that risk factors contributing to alcohol consumption during pregnancy may differ by maternal age.

Aim: To develop an ultrasonographic severity scoring of non-immune hydrops in order to predict perinatal outcomes in women with non-immune hydrops. Methods: The study population consisted of pregnant women who were admitted and delivered with the diagnosis of fetal non-immune hydrops and singleton gestation. Cases were divided into “perinatal survivor” and “perinatal non-survivor” groups. Perinatal non-survivor cases were defined as those with stillbirth or neonatal death ≤28 completed days after birth. The presence of an abnormal fluid collection in each body compartment, such as subcutaneous edema, pleural effusion, pericardial effusion, or ascites was assigned a score of 1 point per each body compartment, and the absence of abnormal fluid collection was scored as 0 point. The total number of abnormal fluid collections was converted to a numeric score, which was called the ultrasonographic severity scoring of non-immune hydrops (USNIH). Results: Perinatal death occurred in 46.5% (20/43) of the cases of non-immune hydrops. USNIH in patients of the non-survivor group was significantly higher than that in those of the survivor group [non-survivor group 3 (2–4) vs. survivor 2 (2–3); median (range); P<0.05]. Perinatal mortality rates were higher in patients with USNIH ≥3 points than in those with USNIH of 2 points (67% vs. 13%, P<0.005). This difference remained significant after adjustment for confounding variables. When confining analysis to those with idiopathic non-immune hydrops, women in the perinatal non-survivor group had significantly higher USNIH score than those in the perinatal survivor group, and this difference remained significant after adjustment. Conclusions: Our USNIH system may be a reliable predictive marker for perinatal outcomes in cases of non-immune hydrops, especially in idiopathic hydrops during the antenatal period.

Background: Considerable controversy continues to surround the management of severe preeclampsia and HELLP syndrome. Experts, researchers, and those published in the field were surveyed about their specific practices. Materials and methods: An extensive literature search was undertaken to identify the cohort of authors with recent publications on the subjects of preeclampsia (2009–2012) and HELLP syndrome (2005–2012). Online surveys were sent to all authors using the email addresses found in their publications. Results: Surveys were delivered by email to 363 authors of preeclampsia publications and 91 authors of HELLP syndrome publications. Completed surveys were received from 61 (13.4%) of the group. Except for consensus about the indication of corticosteroids for the enhancement of fetal lung maturation, there was considerable variation in corticosteroid practice and anesthesia techniques. Conclusions: A marked diversity in practice characterized the clinical care rendered by experts in the field of preeclampsia and HELLP syndrome. Thus, there is an urgent need for well-designed and executed prospective clinical trials to improve the evidence for best consensus practice in this area of obstetrical medicine.

Objectives: The aim of this study was to evaluate the inter- and intra-observer variabilities in the cervical length (CL) measurement by transvaginal ultrasound (TVU) in the first and second trimesters of pregnancy. Materials and methods: A total of 55 singleton pregnant women were evaluated in the first or second ultrasound. Each patient was blindly evaluated by three of the four observers who performed three measurements each. Results: In the first and second trimesters, patients were evaluated at 12.3 weeks (mean) and 21.3 weeks (mean), respectively. The intra-class correlation coefficients (ICC) between observers in the first and second trimesters were 0.76 and 0.72, respectively, and the ICCs within observers were 0.889 and 0.899, respectively. In both trimesters, the main source of variance was the patient and the second source of variance was the interaction, Patient×Observer (12.0% and 13.5%, respectively). The observer and measurement explained a small proportion of variance in both trimesters (1.4% and 0.4%, respectively in the 1 st trimester, and 3.3% and 0%, respectively in the 2 nd trimester). The residual variances were 10.6% and 11.2%, and the standard errors of measurement were 1.78 mm and 1.82 mm for the first and second trimesters, respectively. Conclusions: TVU is a reliable and reproducible method by which to predict preterm birth in both the first and second trimesters.

Objective: To evaluate whether medical personnel differ from the general population in obstetrical and perinatal outcomes. Materials and methods: The participants comprised 46 physicians and 116 nurses employed at one medical center who gave birth in its maternity hospital. General medical and obstetrical data on their latest (“index”) pregnancy and delivery were extracted from real-time computerized patient files. The control group included 162 women who gave birth during the same period in the same hospital. Results: The study group had significantly more deliveries, cesarean sections, and terminations of pregnancy prior to the index pregnancy. The medical personnel conceived significantly more often with assisted reproductive technologies (ART) (18.8% vs. 8% for controls, P<0.05), and had significantly more obstetrical complications, i.e., premature contractions, gestational diabetes mellitus, preeclamptic toxemia, and 2 nd /3 rd trimester bleeding or chorioamnionitis (42.5% vs. 29% for controls, P<0.05). The rate of vaginal birth after cesarean delivery (VBAC) was lower in the study group (22.2% vs. 33.3% for controls, P=0.03). There was no difference in gestational age at delivery, birth weight, or adverse neonatal outcome. Conclusions: Medical personnel utilized ART more frequently and had more pregnancy complications as well as a lower incidence of VBAC than non-personnel. Neonatal outcomes were similar for both groups.

Aims: Obstructive sleep apnea (OSA) is associated with placenta-mediated adverse clinical outcomes. We aimed at comparing placenta-secreted proteins, such as first and second trimester Down syndrome screening markers which have been linked to preeclampsia, and markers of angiogenesis in pregnant women with OSA, and pregnant controls at low risk for OSA. Methods: A case-control study of pregnant women with OSA and controls at low risk for OSA was performed. Levels of first and second trimester markers were reported as multiple of median (MoM), and adjusted for body mass index (BMI). Stored samples were tested for markers of angiogenesis and adjusted for gestational age, BMI, and chronic hypertension. Results: A total of 24 women with OSA and 166 controls had screening markers. BMI was higher in cases compared to controls, P=0.01. MoM levels of placenta associated plasma protein-A (PAPP-A) were significantly lower in cases versus controls, even after adjusting for BMI (0.52 IQR 0.48 vs. 1.01 IQR 0.63, P=0.009). The ratio of soluble vascular endothelial growth factor receptor 1 to placental growth factor was significantly higher in cases than controls, even after adjusting for confounders (4.42 IQR 2.52 vs. 2.93 IQR 2.01, P=0.009). Conclusion: Circulating placenta-secreted glycoproteins and markers of angiogenesis are altered in pregnant women with OSA.

Objective: This study aims to evaluate the value of increasing inflammation in predicting gestational diabetes mellitus (GDM). Materials and methods: Subjects in this cross-sectional study included 302 GDM and 310 normal pregnancies before 20 weeks. Sociodemographic and pregnancy characteristics as well as blood parameters were acquired by maternal health booklet, medical records and laboratory information systems. Blood cell parameters were compared between the two groups by independent sample t -tests. Multivariate logistic regression, χ 2 -test, receiver operator characteristic curve (ROC), and Fisher’s linear discriminant were performed to analyze the screening effects of variables in developing GDM. Results: Women with GDM had significantly higher neutrophil (NEU), lymphocyte (LYM), platelet (PLT) and erythrocyte (RBC) counts, and were positively correlated with GDM. NEU (odds ratios, OR, 1.22) and LYM (OR, 2.01) were independently associated with the development of GDM (P<0.001). The OR of the mean platelet volume (MPV) and mean cell volume (MCV) were 0.84 and 0.92, respectively (P<0.01 for both). The efficiency of Fisher’s equations in correctly classifying cases of GDM from 4 to 20 weeks of gestation was 70.06%. Conclusions: Maternal WBC, RBC, and PLT counts are important correlates of GDM. Increased volume of RBC and PLT might protect pregnant women from development of GDM.

Aims: Peripartum cardiomyopathy (PPCM) is an infrequent form of cardiomyopathy causing significant maternal morbidity and mortality. We aimed to evaluate the risk factors, characteristics and prognosis of PPCM during the index and subsequent pregnancies. Methods : A retrospective cohort of 36 women with PPCM in a tertiary medical center was analyzed and compared with 10,370 women who gave birth during a single calendar year at the same institution. Results: Women diagnosed with PPCM were older (mean 33.5 years) than controls. A significantly higher proportion were primiparous (63.9%), carried multifetal pregnancies (33.3%) and had hypertensive pregnancy complications (38.9%). Thirty-six percent of PPCM patients conceived with in vitro fertilization, and six of them received ovum donation. Twenty-two women had severe left ventricular dysfunction at diagnosis, and these women tended to remain with residual disease, compared with women with milder ventricular dysfunction at diagnosis. Eight patients recovered completely within 2 weeks of diagnosis. Women who recovered early (n=8) had significantly higher ejection fractions on last follow-up compared with women (n=28) who had late or partial recovery. Nine women had 14 additional pregnancies; of them eight women had normal cardiac functions on subsequent pregnancy. Conclusions : Risk factors for peripartum cardiomyopathy include primiparity, hypertension and multifetal pregnancies. Assisted reproduction techniques are not independently associated with PPCM but rather through other risk factors for PPCM. The degree of cardiac dysfunction at diagnosis and time to recovery are important prognostic factors.

Aims: The aim was to evaluate whether assisted reproductive technology (ART) affects the development of the fetal central nervous system (CNS). Methods: This study was carried out on women with singleton pregnancies, including 427 women who became pregnant by ART and 32,859 women with natural conceptions (NCs). The cavum septum pellucidum (CSP) width, transverse cerebellar diameter (TCD), cisterna magna (CM) depth, and lateral ventricle width were measured by ultrasound for 72 normal ART fetuses and 201 normal NC fetuses. The malformation rate of CNS was determined for both groups. Results: In both groups, significant positive correlations with gestational age were found for CSP width (ART: r=0.7841, NC: r=0.7864; P<0.0001) and for TCD (ART: r=0.7698, NC: r=0.6926; P<0.0001). However, neither CM depth nor lateral ventricle width showed a significant correlation with gestational age. None of the measured parameters showed a statistically significant difference between the two groups. The CNS malformation detection rate was 1.2% (5/427) in ART fetuses and 0.9% (296/32,859) in NC fetuses. It did not reach statistical significance (P>0.05). Conclusions: The development and malformation rate of the fetal CNS is not significantly different between ART and NC fetuses, thus, ART does not affect the development of the fetal brain.

Objectives: This work aimed to analyze a single large representative population to determine racial/ethnic differences in the prevalence of congenital anomalies (CA). Design: This is a population-based comprehensive analysis of racial/ethnic differences in the prevalence of CA diagnoses. We reviewed all live births in the 2008 Nationwide Inpatient Sample (NIS) database and determined the birth prevalence of 55 selected CA diagnoses in Caucasians. We then calculated the relative risk of these CA diagnoses in African American, Hispanics, and Asians relative to Caucasians. Result: Overall CA prevalence was 29.2 per 1000 in a cohort of 1,048,252 live births, of which 51% were Caucasians. Compared with Caucasians, risk of overall CA was lower in African Americans (RR=0.9, CI: 0.8–0.9) and Hispanics (RR=0.9, CI: 0.8–0.9). Risk of overall CA was similar in Caucasians and Asians. Relative to the Caucasians, African Americans had lower risk of cardiac, genitourinary, and craniofacial CA but higher risk of musculoskeletal anomalies. Hispanics had lower risk of genitourinary and gastrointestinal CA. Asians had higher risk of craniofacial and musculoskeletal CA. Conclusions: Observed racial/ethnic differences in risk of CA may be related to genetic susceptibilities, cultural or social differences that could modify exposures, or many potential combinations between susceptibilities and exposures.

Aim: Intravascular pressure-induced vasoconstriction (myogenic constriction) is central to renal blood flow autoregulation. At term, kidney maturation is functionally incomplete. Premature neonates are at risk of kidney dysfunction. However, it is unclear whether renal artery myogenic constriction is altered after preterm birth. Here, we compared renal artery myogenic constriction in full-term and preterm pigs during the first week of life. Methods: We investigated myogenic constriction in small interlobular arteries isolated from the kidneys of pigs delivered at term and at 91% of term (with and without 96 h of neonatal intensive care). Results: Cross-sectional area, media/lumen ratio, and luminal diameter measured under passive conditions were similar in arteries from full-term and preterm pig kidneys. An acute elevation in intravascular pressure from 20 to 100 mm Hg increased arterial wall tension and induced steady-state constriction of the arteries. However, arteries isolated from newly born preterm pigs (within 24 h) developed greater myogenic tone and lower active wall tension compared with arteries from full-term and 4-day-old preterm neonates. Pressure-induced elevation in intracellular Ca 2+ was also larger in arteries from newly born preterm pigs compared with full-term and 4-day-old preterm pigs. Conclusion: Myogenic constriction is elevated in newly born preterm pigs. Our data also suggests that postnatal kidney maturation may modulate renal blood flow autoregulation.