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Journal: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

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Objective: Recent progresses in fetal surgery have raised concern on fetal pain, its long-term consequences and the risks of sudden fetal movements induced by pain. In several studies, surgeons have directly administered opioids to the fetus, while others have considered sufficient the maternally administered analgesics. We performed a review of the literature to assess the state of the art. Methods: We performed a PubMed search to retrieve the papers that in the last 10 years reported studies of human fetal surgery and that described whether any fetal analgesia was administered. Results: We retrieved 34 papers. In three papers, the procedure did not hurt the fetus, being performed on fetal annexes, in two papers, it was performed in the first half of pregnancy, when pain perception is unlikely. In 10 of the 29 remaining papers, fetal surgery was performed using direct fetal analgesia, while in 19, analgesia was administered only to the mother. In most cases, fetal direct analgesia was obtained using i.m. opioids, and muscle relaxant. Rare drawbacks on either fetuses or mothers due to fetal analgesia were reported. Conclusion: Fetal direct analgesia is performed only in a minority of cases and no study gives details about fetal reactions to pain. More research is needed to assess or exclude its possible long-term drawbacks, as well as the actual consequences of pain during surgery.

Concepts: Pregnancy, Embryo, Fetus, Uterus, Surgery, Pain, Abortion, Spina bifida

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Intrauterine Growth Retardation (IUGR) is defined as a rate of growth of a fetus that is less than normal for the growth potential of the fetus (for that particular gestational age). Small for Gestational Age (SGA) is defined infant born following IUGR, with a weight at birth below the 10th percentile.Suboptimal fetal growth occurring in IUGR fetuses is an important cause of perinatal mortality and morbidity. The acute neonatal consequences of IUGR include metabolic and hematological disturbances, and disrupted thermoregulation; in addition, respiratory distress (RDS), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP) may contribute to perinatal morbidity. Metabolic disturbances are related to glucose and fatty acid metabolism. It is well-known that individuals who display poor growth in utero are at significantly increased risk for type 2 diabetes mellitus (T2DM), obesity, hypertension, dyslipidemia, and insulin resistance (the so-called metabolic syndrome, MS). MS ultimately leads to the premature development of cardiovascular diseases. In addition, short stature in children and adults, premature adrenarche, and the polycystic ovarian syndrome (PCOS) are endocrinological sequelae of IUGR. (8) Early onset growth delay and prematurity significantly increase the risk for neurological sequelae and motor and cognitive delay.Future prospective studies need to investigate risk factors for infants who are SGA. If reliable prediction can be achieved, there is potential to reduce future perinatal morbidity and mortality, and long term consequences among SGA babies.

Concepts: Pregnancy, Infant, Nutrition, Embryo, Fetus, Diabetes mellitus type 2, Diabetes mellitus, Obesity

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Abstract Objective. In general the analytical epidemiological studies evaluated cases with congenital heart defects together. However, different congenital heart defect entities have different etiology, and in the vast majority of patients the underlying causes are unclear. Thus the objective of the study was to evaluate the possible etiological factors in the origin of single ventricular septal defect (VSD) after surgical intervention or lethal outcome, i.e. as homogeneous as possible. Method. In the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities acute and chronic maternal diseases with related drug treatments and pregnancy supplements in early pregnancy were evaluated in the mothers of 1,661 cases with isolated/single VSD and their 2,534 matched and 38,151 all controls without defect, and 19,833 malformed controls with other isolated non-cardiac defect. Results. There was a higher risk of VSD in the children of mothers with high fever related influenza during the critical period of VSD and this risk was limited by antifever therapy. In addition paroxysmal supraventricular tachycardia and epilepsy treated with anticonvulsant drugs associated with higher risk of VSD. Finally the high doses of folic acid alone in early pregnancy Conclusions. H high fever related maternal diseases may have a role in the origin of VSD which is preventable with antifever drug therapy, and the high doses of folic acid in early pregnancy were able to reduce the risk of VSD.

Concepts: Epidemiology, Down syndrome, Congenital heart defect, Congenital heart disease, Ventricular septal defect

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Objective: An association between Helicobacter pylori (H. pylori) and thrombocytopenia has been demonstrated in the literature in a non-pregnant population. The purpose of this study was to determine whether or not there is a similar association in the third trimester of pregnancy in a Hispanic population. Methods: This is a secondary analysis of 82 pregnant Hispanic women with and without hyperemesis gravidarum who underwent serologic evaluation for H. pylori IgG. Results of complete blood counts obtained in the third trimester were analysed for thrombocytopenia. Results: Of the 82 subjects who had H. pylori testing, 54 subjects had both serum H. pylori IgG results and third trimester platelet levels. The prevalence of thrombocytopenia was 11.1% (6/54). Thirty-six subjects were seropositive for H. pylori IgG and 18 subjects were seronegative. Of the 36 subjects who were H. pylori seropositive, four (11.1%) developed thrombocytopenia compared to three of 18 (16.7%) H. pylori seronegative subjects (P = 0.67). There was no difference between the groups in their mean platelet values (205 K/cu mm vs. 212 K/cu mm, P = 0.69). Conclusions: In this limited study, we found no association between H. pylori and thrombocytopenia in the pregnant Hispanic population.

Concepts: Pregnancy, Platelet, Gastroenterology, Helicobacter pylori, Helicobacter, Thrombocytopenia, Urease, Giulio Bizzozero

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Abstract Objective: The aim of the study is to evaluate the application of Neurally Adjusted Ventilatory Assist (NAVA) in the respiratory weaning of patients affected by congenital diaphragmatic hernia (CDH). Methods: We analyzed the NAVA weaning in 12 neonates affected by CDH, relating the effectiveness of the electrical activation of the diaphragm (EAdi) signal to the type of CDH repair (with or without patch), the size of the patch, the stomach and His angle position, and the trend evaluation of some cardio-respiratory parameters with NAVA compared to pressure-support-ventilation (PSV). Results: 5 neonates submitted to primary repair showed a regular EAdi signal and were successfully weaned with NAVA. Of the 7 patients submitted to patch repair, 5 operated with patch limited to the diaphragmatic postero-lateral area had an active EAdi signal that permitted weaning with NAVA. Only in 2 neonates with hemidiaphragm agenesis was NAVA not feasible due to the impossibility to capture the EAdi signal. Compared to PSV, NAVA allows a significant improvement of oxygenation-linked indexes and paCO(2), while PIP is reduced. Conclusion: Neonatal CDH with a postero-lateral diaphragmatic defect allows the NAVA catheter to obtain a correct EAdi signal and develop a viable NAVA ventilation. The lower risk of lung injury in NAVA appears compatible with current ventilatory strategies considered useful in CDH.

Concepts: Milk, Breastfeeding, Respiratory system, Thoracic diaphragm, Diaphragm, Respiration, Congenital diaphragmatic hernia, Weaning

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Abstract Objective: The etiology of jaundice in otherwise healthy breastfed newborns that can present as early-onset exaggerated physiologic jaundice, or late breast milk jaundice (BMJ), is not yet entirely understood. This study tested the hypothesis that molecular marker for Gilbert’s syndrome (GS), UGT1A1 TATA-box polymorphism, is associated with this disorders. Methods: We have investigated the UGT1A1 polymorphism frequency and its relation to severity of hyperbilirubinemia and jaundice duration among 220 exclusively breastfed term newborns; 57 of them with non-physiologic hyperbilirubinemia (NH), and 163 with BMJ, and in 187 healthy controls. Results: Significant differences in TA7/7 genotype frequency were established. The highest frequency was observed among the newborns with BMJ (42.0%), intermediate in the NH group (24.6%), while the controls had the lowest TA7/7 frequency (12.8%). Linear increase in TA7/7 frequency was observed depending on the duration of jaundice, peaking at 42.4% in newborns with the longest jaundice duration. Positive correlation between the serum bilirubin levels and the TATA-box length was established in all groups. Conclusion: This study provides evidence that UGT1A1 TATA-box polymorphism is an important risk factor for developing jaundice in term breastfed newborns, presented as either early non-physiologic hyperbilirubinemia or breast milk jaundice. These results further support the original Odell’s idea of neonatal jaundice as an early presentation of GS.

Concepts: Infant, Milk, Hepatology, Bilirubin, Neonatal jaundice, Jaundice, Gilbert's syndrome, Crigler-Najjar syndrome

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Abstract Objective: To evaluate the post-partum maternal cardiac function in patients with history of severe preeclampsia. Methods: A series of women with previous singleton pregnancy complicated by severe preeclampsia underwent transthoracic echocardiography at 6-12 months from delivery. A group of women with previous uncomplicated pregnancy was selected as controls. Results: 16 women with history of severe preeclampsia were enrolled in the study group whereas 18 patients were selected as controls. In the study group systolic (P=0.002) and diastolic blood pressure (P=0.044) were significantly higher. Significant differences were observed in systolic left ventricular (LV) parameters, such as cardiac output (P=0.034), left ventricular mass indexed to BSA (P=0.024) and longitudinal contraction, expressed by tissue Doppler (TD) S1 wave, which resulted relatively impaired in former preeclamptic women (P=0.049). As regards as diastolic parameters, pulsed Doppler A-wave velocity was increased (P=0.036). TD E-wave velocity was significantly lower in study group (P<0.001) and E/E1 ratio (E=peak early diastole transmitral wave velocity / E1=peak early diastolic velocity at mitral valve annulus at TD) was higher respect to controls (P<0.001). Conclusions: LV contractility and diastolic function, although within normal reference ranges, show slight but significant impairment among women who experienced a severe preeclampsia. TD seems to be a sensible tool to identify these precocious signs of potential LV dysfunction.

Concepts: Blood, Cardiology, Doppler echocardiography, Echocardiography, Blood pressure, Ventricle, Mitral valve, Cardiac cycle

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Abstract Objective: Cesarean section is associated with more blood loss than vaginal delivery. This could increase the risk of morbidity and mortality especially among anemic women.The objective of the trial is to assess the possible effect of tranexamic acid on blood loss during and after elective cesarean section. Methods: We conducted a randomized controlled trial at Women’s Health Hospital, Assiut University, Assiut, Egypt. All pregnant women with singleton fetus planned to have elective cesarean section at ≥37wks gestation were randomized to receive 1 gm tranexamic acid slowly intravenously over10 minutes before elective cesarean section group or not.Blood loss was measured during and for two hours after operation. Any side effects, complications, medications, changes in vital signs and duration of hospital stay were recorded. This study is registered, number ACTRN12612000313831 Results: Seven hundred and forty women were randomized (373in study group and 367 in control group). Mean total blood loss was 241.6 (SE 6.77) ml in the tranexamic acid group versus 510 (SE 7.72) ml in the control group. The mean drop in hematocrit and hemoglobin levels werestatistically significantly lower in the tranexamic acidgroup than in the control group. There were no statistically or clinically significant differences in other outcomes. Conclusions: Pre-operative use of tranexamic acid is associated with reduced blood loss during and after elective cesarean section.This could be of benefit for anemic women or those who refuse blood transfusion.

Concepts: Pharmacology, Childbirth, Epidemiology, Clinical trial, Blood, Randomized controlled trial, Effectiveness, Blood transfusion

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Abstract Objective: To determine whether perineal massage during the second stage of labor using oil enriched with vitamins, increases the chances of delivering with an intact perineum as compared to perineal massage using pure liquid wax. Methods: A prospective, randomized, double-blind study was conducted. Women were assigned to liquid wax (jojoba oil) vs. purified formula of almond and olive oil, enriched with vitamin B1, B2, B6, E and fatty acids. The caregivers used the oils during the second stage of labor. Results: A total of 164 women undergoing vaginal delivery were recruited. No significant differences regarding perineal lacerations, number of sutures and length of suturing were noted between the two groups. Likewise, while analyzing separately nulliparous and multiparous women, no significant differences were noted. Controlling for birth-weight >4000 grams, using the Mantel-Haenszel technique, no association was noted between perineal lacerations and the type of oil used (weighted OR=0.9, 95% CI 0.3-2.4; p=0.818). Conclusion: The type of the oil used during the second stage of labor for prevention of perineal tears has no effect on the integrity of the perineum. Accordingly, it seems that there is no perfect oil.

Concepts: Childbirth, Water, Fat, Vitamin, Wax, Thiamine, Olive oil, Oil

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Abstract Objectives: To find an effective way to predict cesarean section (CS) before induction of labor. Methods: Nulliparous women at ≥41 weeks of pregnancy were enrolled in study. Bishop score, cervical length, posterior cervical angle, quantification of the cervical stromal echogenity by tissue histograms and opening of the internal cervical os (Funnelling) were recorded. The vaginal delivery and CS groups were then compared in terms of the clinical and ultrasonographic cervical findings. Results: Bishop score, cervical length, posterior cervical angle and funnelling were significant predictors of CS whereas no such relationship existed for the quantitave echogenity of the cervical stroma. Although the difference was not statistically significant, the area under the curve was higher for the Bishop score than the sonographic cervical length and posterior cervical angle in the prediction of all cesarean sections. The best cut-off values to predict CS for Bishop score, cervical length and posterior cervical angle were <5, >27 mm and <98 degrees respectively. Combination of all three parameters had a sensitivity of 83.3%, specificity of 100 %, positive predictive value (PPV) of 100 % and negative predictive value (NPV) of 82% for the prediction of CS. Conclusions: In nulliparous women with prolonged pregnancy the Bishop score predicts the need for CS better than the ultrasonographic assessment of the cervix.

Concepts: Childbirth, Positive predictive value, Obstetrics, Cervix, Epidural, Caesarean section, Labor induction, Pre-eclampsia