Normal Gestation Research Articles

P-757 Clinical and neonatal outcome of single vitrified-warmed blastocyst transfer with complete zona pellucida removal using laser-assisted hatching

Abstract Study question Complete zona pellucida (ZP) removal using laser assisted hatching can improve clinical and neonatal outcome in single vitrified-warmed blastocyst transfer (SVBT) cycle? Summary answer Implantation rate, clinical pregnancy rate and live birth rate can be improved by complete removal of zona pellucida, whereas no impact on neonatal outcomes. What is known already Assisted hatching (AH) technique widely used in assisted reproductive technology for improving clinical outcome in frozen embryo transfer (FET), which could impair successful embryo hatching out of the zona pellucida (ZP) due to ZP hardening during vitrification-warming. The zona thinning and drilling methods of AH doesn’t affect clinical, live births outcomes and it could increase monozygotic twin birth, risk of placenta associated diseases. But recent studies showed that the complete removal of ZP may increase the chance of blastocyst adhesion and outgrowth afterwards, which required to be proven. Study design, size, duration Retrospective study data collected from July 2015 to November 2019 included SVBT in the Ojinmed IVF center. We divided into 2 groups as follows: case group 160 (randomly selected complete removal of ZP) and control group 160. The clinical outcomes were implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), miscarriage and neonatal outcomes including monozygotic twin, birth baby sex, birth weight, height and gestational weeks. All parameters were compared between two groups. Participants/materials, setting, methods 320 vitrified blastocyst transfer cycles in 215 patients underwent a clomiphene-based minimal ovarian stimulation protocol or drug-free natural cycles. All embryos were vitrified-warmed by Cryotop method (Kitazato, Japan). Complete removal of ZP selected an survived blastocysts after warming and used an immediate laser drilling (Laser: 1.8-2.2 ms, Octax NaviLaseTM) in perivitelline space. And gently glass pipetting done for complete removal of ZP. Statistical analysis performed by Chi-square test and logistic regression analysis using STATA 12. Main results and the role of chance A total 320 SVBT cycles, including ZP completely removed 160 cycles and control 160 cycles. In analysis of the patient's age, fertility causes and fertilization methods were not significant (p < 0.05) between two groups. The IR (55.2 % and 66.2 %, p < 0.01), CPR (39.3 % and 52.5 %, p = 0.01) and LBR (29.3 % and 43.7 %, p < 0.01) are highly correlated between the control and the completely removal of ZP group, respectively. In multivariable logistic regression analysis showed the completely removal of ZP group had significance for IR (aOR 0.54, CI 95 % 0.31-0.93, p = 0.02), CPR (aOR 0.56, CI 95 % 0.32-0.96, p = 0.03) and LBR (aOR 0.56, CI 95 % 0.32-0.99, p = 0.048), which adjusted by patient age, blastocyst grade and vitrification day. Miscarriage rate didn’t show significance (23.8% and 21.4%, p = 0.73) between groups. The neonatal outcomes including monozygotic twin, sex of the births, average gestation week and birthweight were non significant (p < 0.05) between two groups (49 for control group and 66 for case group) children. Limitations, reasons for caution The result of the current retrospective study is limited to data from a single IVF center. Wider implications of the findings Our study suggests that complete removal of ZP using laser assisted can improve clinical outcomes including implantation, clinical pregnancy and live birth after SVBT. And it may doesn’t affect to miscarriage rate and neonatal outcome. Trial registration number not applicable

O-008 Low grade blastocysts result in healthy live births and should not be discarded

Abstract Study question Does transfer of low grade blastocysts results in acceptable live birth rates the birth of healthy babies? Summary answer While BC/CB/CC blastocysts have a reduced chance of live birth compared with AA/AB/BA/BB blastocysts, the absolute chances are still reasonable. What is known already Transfer of poorer quality embryos and blastocysts result in lower live birth rates, though to what extent is unclear, nor if there is an absolute threshold below which live births are very rare or even do not occur. Further, the developmental competence of the inner cell mass (ICM) or trophectoderm (TE) could at least theoretically impact the pregnancy and/or the health of the baby. Many clinics do not transfer or freeze poor quality embryos and blastocysts, and prefer to submit the patient to a further stimulation cycle. Study design, size, duration We performed a retrospective analysis of 10,978 couples undergoing singleton blastocyst transfers between 2009 and March 2020. We included all single blastocyst transfers for which there was complete data on blastocyst quality, singleton or twin births, birthweight and gestation at delivery, irrespective of blastocyst grading, female age, cause of infertility, ovarian response or endometrial thickness. We recorded live birth rates, birth weight and gestational age. Participants/materials, setting, methods Data from 14 clinics in 3 countries, 8 from China, 5 from New Zealand, and 1 from Australia were included in the final dataset. We compared the impact of blastocyst grading using multiple logistic regression. Blastocyst grading was based on the Gardner classification, in which the first letter denotes the grade of the inner cell mass (A is best), and the second letter the grade of the trophectoderm. Main results and the role of chance Overall, 10,978 single blastocyst cycles resulted in 4,261 live births (38.8%) (4195 singletons and 132 twins). Live birth rates were 47% after transfer of AA blastocysts (n = 2306); 42% after AB/BA (n = 2088); 33% after BC (n = 1973); 25% after CB (n = 715) and 14% after CC (n = 117). There were too few AC (n = 27) or CA (n = 12) blastocysts to include in the analysis. The odds of live birth for BC/CB/CC blastocysts compared with AA/AB/BA blastocysts, vary between 0.8 and 0.9. The live birth rate appears to be more dependent on ICM quality (C grade, n = 844, 23.2%) rather than TE quality (C grade, n = 2117, 32.1%), with the odds of live birth 0.43 and 0.57 respectively compared to A grade ICM or TE. The average birth weight (singleton only) was 3336.9+/-570.3 g (range 3323 to 3386 g), and the average gestation at delivery (singleton only) was 38+6+/-2.0 weeks (range 38+2 to 39+1). There was no significant difference for birth weight or gestational age at delivery between blastocysts of different grades. Limitations, reasons for caution This was a retrospective study. Grading was based on inner cell mass and trophectoderm and not on degree of expansion, or on day of transfer. It is likely that higher quality blastocysts were transferred first, in a fresh cycle, and poorer quality blastocysts frozen for later transfer. Wider implications of the findings The most important finding is that reasonable live birth rates are obtained in CC-blastocysts. We therefore advocate that CC-blastocysts should be replaced or frozen for later transfer. It is reassuring that there was no impact of blastocyst quality on birth weights or gestational age at the time of delivery. Trial registration number Not applicable

P-546 The structure of genome variations at CNV level differs in recurrent and sporadic pregnancy loss

Abstract Study question Whether the CNV load differs in fetal tissues of miscarriages from families with recurrent and sporadic pregnancy loss? Summary answer In RPL group duplications are more common than deletions, de novo variants than inherited ones. Pathogenic CNVs (dup16p11.2, del22q13, dupXq28) were found in both groups. What is known already Data on CNVs in tissues of miscarriages can be found in more than 24 articles. Altogether 7732 samples were analyzed by aCGH and NGS; 988 CNVs of uncertain clinical significance were found in 636 samples (8.2%). The origin was determined for 130 variants: 85 maternal (65.4%), 34 paternal (26.2%), 11 de novo (8.4%) CNVs. No aberration unambiguously associated with miscarriage was found so far. Comparative analysis of CNVs in family trios with recurrent and sporadic miscarriage may help to characterize structural genome variations associated with embryo lethality both from embryo and parental side. Study design, size, duration Identification of structural genome variations (SGV) at the CNV level was performed by aCGH-analysis for family trios: mother, father and fetal. Characteristics of SGV associated with embryo lethality included such parameters as CNV type (deletion/duplication) and its origin. It was assumed that the structure of genomic variability may differ in recurrent pregnancy loss (RPL) and sporadic pregnancy loss (SPL) both in embryonic tissues and in parents. Participants/materials, setting, methods Eleven family trios (7 RPL and 4 SPL) were included in the research. Standard G-banding was performed for all abortion samples to exclude aneuploidy. STR-haplotyping for the SRY gene was used to exclude maternal cell contamination. Finally all samples were analyzed for CNVs using SurePrint G3 Human CGH+SNP 4 × 180K microarrays (Agilent Technologies). Average gestation age was 7.9 weeks. Average maternal and paternal age was 30.8 and 30.5 years, respectively. Main results and the role of chance In seven and four embryos from RPL and SPL groups 110 and 60 CNVs were identified, respectively. In RPL, there was a tendency towards an increase in the frequency of duplications over deletions (72:38) in comparison to SPL (36:24) (p = 0.5). Duplications prevailed over deletions in five of seven embryos from RPL group; while there were two cases of each combination in SPL. One can suggest that some SPL cases can move into RPL group over time. De novo variants prevailed over inherited in the RPL group (76:43) and inherited prevailed in the SPL (32:28) (p < 0.05). This result allows to suggest that in cases with RPL there may be some common genetic/epigenetic factor predisposing to CNV generation either in primordial germ cells or during early blastomere cleavage. Among the inherited variants in the RPL group there were 24 maternal and 8 paternal CNVs, while in the SPL – 18 and 14 (p = 0.1). In both groups pathogenic CNVs associated with syndromes characterized by neurodevelopmental disorders (NDD) in children were found (del22q13, dupXq28 – in RPL group, dup16p11.2 – two cases in SPL). Presumably, such aberrations may explain a high risk of NDD in a child of a woman with RPL/SPL (PMID:30058166, PMID:33580539). Limitations, reasons for caution No one CNV unambiguously associated with pregnancy loss has been described so far. Possibly, total structural genome variations level should be considered as pathogenic factor for embryo development. There is no adequate algorithm of clinical significance CNV interpretation for the embryonic period. Wider implications of the findings Prenatal or preimplantation genetic testing should be considered if one of the parents is a carrier of CNV associated with microdeletion/microduplication syndrome. This study was supported by the Russian Science Foundation № 21-65-00017, https://rscf.ru/project/21-65-00017/. Trial registration number Russian Science Foundation № 21-65-00017

Renin-angiotensin system in normal pregnancy and in preeclampsia: A comprehensive review.

The activation of the Renin Angiotensin System (RAS) is required during pregnancy and it seems that RAS dysfunction has some important effects on pathological pregnancy conditions, including preeclampsia (PE). The objective of this review is to summarize and to discuss the role of the RAS in normal pregnancy and in PE. We found evidence that the RAS is important for the evolution of pregnancy under physiological conditions and plays an important role in the pathogenesis of PE. In normal gestation, almost all circulating components of RAS are increased and there is a general state of non-reactivity to the vasoconstrictor actions of Angiotensin (Ang) II. In PE, changes in the circulating levels of RAS components occur, especially with an intense decrease in the levels of Ang I, Ang II and Ang-(1-7). Our findings endorse the idea that PE is a disease whose cornerstone relies on altered placental physiology. There are high tissue levels of Ang II type 1 receptor (AT1R) in the musculature of the blood vessels and in the placenta, generating a state of increased sensitivity to the vasoconstrictor action of Ang II. AT1R autoantibodies (AT1R-AA) might be one of the key points for the vicious cycle of PE, as these molecules are synthesized in situations of hypoxia and enhance placental vasoconstriction, causing even more hypoxia. Further studies are needed to investigate the role of circulating RAS, uteroplacental RAS and local RAS molecules from other tissues related to the pathogenesis of PE.

Evaluation of the hemostasis system in pregnant women with placental dysfunction by the method of rotational thromboelastometry

The objective: to evaluate the standard indicators of thromboelastometry in pregnant women with placental dysfunction. Materials and methods. Venous blood samples of 26 healthy pregnant women (control group) and 50 patients with placental dysfunction (main group, persons 19–40 years old) were examined. The average gestation period at the time of the study was 29.5±7.2 and 32.9±4.4 weeks, respectively. Standard coagulation tests (coagulogram) and rotational thromboelastometry were performed. Results. Hypercoagulability according to the standard coagulation tests in the women with placental disorders did not correspond to gestational age. No correlation was established between coagulogram parameters, the number of platelets and temogram parameters. According to thromboelastography tests, an increase in clot density is typical for pregnant women with placental dysfunction. Specifically, the results of the fibtem test demonstrated, a statistically significant (p<0.05) increase in clot density at 5, 10, and 20 minutes. Such indicators of fibrinogen synthesis and the fibrin polymerization process indicate the formation of a denser clot in the patients with placental dysfunction. In addition, the MCF indicator, which informs about the maximum density of the clot, is significantly higher in the pregnant women with placental dysfunction compared to the control group. Conclusions. Disorders of coagulation homeostasis in the form of clot formation of increased density play an important role in the pathogenesis of placental dysfunction. This is one of the causes of hemodynamic disorders in the utero-placental and feto-placental blood flow. Thromboelastography, in contrast to the basic coagulation tests of the standard coagulogram, is a more informative method of assessment the coagulation ability of blood in the pregnant women with placental dysfunction.

Effect of Maternal HIV Infection on Infant Development and Outcomes

Early life represents a period of profound immunological development and heightened susceptibility to infectious disease. The developmental trajectory over this period is influenced by a number of factors, including gestational age, mode of delivery, mode of feeding, microbiome development, and environmental exposures. There are also several maternal factors that have been shown to have a negative effect on both immune development and clinical outcomes, including maternal infection and inflammation. Studies have associated maternal HIV infections with an increase in infectious morbidity and mortality and decreased growth measures among their HIV-exposed uninfected (HEU) offspring. Among HEU infants, socioeconomic factors, maternal nutrition, maternal viral load, and maternal inflammation have also all been associated with impaired infant immune status and clinical outcomes. However, the mechanisms underlying these observations have not been elucidated and, apart from measures of disease severity, few studies thus far have undertaken in-depth assessments of maternal health status or immune function during gestation and how these influence developmental outcomes in their infants. The lack of a mechanistic understanding of how these gestational influences affect infant outcomes inhibits the ability to design and implement effective interventions. This review describes the current state of research into these mechanisms and highlights areas for future study include; how HIV infection causes the inflammatory trajectory to deviate from normal gestation, the mechanism(s) by which in utero exposure to maternal inflammation influences infant immune development and clinical outcomes, the role of socioeconomic factors as an inducer of maternal stress and inflammation, and maternal nutrition during gestation.

MP14-20 COMPARISON OF THE EFFECT OF ACTIVE SURGICAL TREATMENT OF UROLITHIASIS IN PREGNANT PATIENTS COMPARED WITH SERIAL URETERAL STENTING ON THE PROBABILITY OF NATURAL DELIVERY

You have accessJournal of UrologyCME1 May 2022MP14-20 COMPARISON OF THE EFFECT OF ACTIVE SURGICAL TREATMENT OF UROLITHIASIS IN PREGNANT PATIENTS COMPARED WITH SERIAL URETERAL STENTING ON THE PROBABILITY OF NATURAL DELIVERY Pavel Nizin, Sergey Kotov, and Perov Roman Pavel NizinPavel Nizin More articles by this author , Sergey KotovSergey Kotov More articles by this author , and Perov RomanPerov Roman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002543.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The primary endpoint is to compare the frequency of natural childbirth in the groups undergoing active surgical treatment of urolithiasis and the group of serial ureteral stenting. METHODS: Criteria for inclusion of diagnosed urolithiasis at any stage of pregnancy in patients without abnormalities of the urinary system. Exclusion criteria, independent departure of the stone. The active treatment group underwent endoscopic surgery to get rid of the stone during gestation. The serial stenting group underwent drainage replacement every 4 weeks during the entire period of pregnancy, followed by operations to get rid of the stone after delivery. RESULTS: Active treatment group n=57 average age 27.2 years (±5.2). The average gestation period was 21.1 weeks (±6.8). Distribution by trimester: I-3.6%, II-73.8%, III–22.8%. The average rate of leukocytosis at admission was 10.9*10^9/l (±4.8*10^9/l). Serial stenting group n=56 average age 26.5 years (±6.1). The average gestation period was 20.2 weeks (±7.2). Distribution by trimester: I-3 (5.4%), II-43 (76.8%), III–10 (17.8%). The average rate of leukocytosis at admission was 11.6*10^9/l (±5.1*10^9/l). 7 (12%) patients from the first group were diagnosed with acute obstructive pyelonephritis. These patients were fitted with an internal ureteral stent. In 5 patients, there was an independent discharge of the concretion. These patients were excluded from observation. In the second group, 4 patients were diagnosed with acute obstructive pyelonephritis. An internal ureteral stent was installed in these patients. In 3 patients, against the background of a standing stent, the stone moved away on its own. These patients were excluded from observation. In the first group, the number of delivery was 35, caesarean section-17. In the second group, delivery-23, CS-30.The probability of delivery was estimated using χ2 is 6.070. The critical value of χ2 at the significance level p=0.05 is 3.841. Complications in the first group: grade I-5 (9%), II–7 (13%). Complications in the second group I degree 9 (17%), II – 8 (15%), IIIa - 9 (17%). Comparison of the development of complications was carried out. The value of the criterion χ2 is 12.724. The critical value of χ2 at the significance level p=0.01 is 11.345. CONCLUSIONS: Active disposal of the stone during pregnancy is safe and reduces the likelihood of delivery by cesarean section and the likelihood of developing stent-associated symptoms. Source of Funding: The study was not funded © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e240 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pavel Nizin More articles by this author Sergey Kotov More articles by this author Perov Roman More articles by this author Expand All Advertisement PDF DownloadLoading ...

The diagnosis and management of Cushing's syndrome in pregnancy.

Endogenous Cushing's syndrome (CS) is rarely encountered during pregnancy. Clinical and biochemical changes in healthy pregnancy overlap with those seen in pregnancy complicated by CS; the diagnosis is therefore challenging and can be delayed. During normal gestation, adrenocorticotrophic hormone, corticotrophin‐releasing hormone, cortisol, and urinary free cortisol levels rise. Dexamethasone administration fails to fully suppress cortisol in pregnant women without CS. Localisation may be hindered by non‐suppressed adrenocorticotrophic hormone levels in a large proportion of those with adrenal CS; smaller corticotroph adenomas may go undetected as a result of a lack of contrast administration or the presence of pituitary hyperplasia; and inferior petrosal sinus sampling is not recommended given the risk of radiation and thrombosis. Yet, diagnosis is essential; active disease is associated with multiple insults to both maternal and foetal health, and those cured may normalise the risk of maternal–foetal complications. The published literature consists mostly of case reports or small case series affected by publication bias, heterogeneous definitions of maternal or foetal outcomes or lack of detail on severity of hypercortisolism. Consequently, conclusive recommendations, or a standardised management approach for all, cannot be made. Management is highly individualised: the decision for surgery, medical control of hypercortisolism or adoption of a conservative approach is dependent on the timing of diagnosis (respective to stage of gestation), the ability to localise the tumour, severity of CS, pre‐existing maternal comorbidity, and, ultimately, patient choice. Close communication is a necessity with the patient placed at the centre of all decisions, with risks, benefits, and uncertainties around any investigation and management carefully discussed. Care should be delivered by an experienced, multidisciplinary team, with the resources and expertise available to manage such a rare and challenging condition during pregnancy.

SIRT1 regulates trophoblast senescence in premature placental aging in preeclampsia

IntroductionPremature placental aging is implicated in a number of complications of pregnancy including preeclampsia. A placenta knockout mouse model has shown a relationship between SIRT1, aging and placental dysfunction. The role of SIRT1 in cellular senescence has been extensively studied in various cell types, but its role in trophoblast senescence is almost unknown. MethodsHuman placental samples were obtained from preeclampsia-affected women and healthy controls. The placental aging profiles were assessed by Doppler ultrasound, placental histopathology, and evaluation of senescence- and ECM-related markers. The SIRT1 expression pattern relevant to placental aging profiles was studied in premature aging placenta with preeclampsia (32–37 weeks gestation, n = 10) and healthy controls (37–40 weeks gestation, n = 10). Using cell culture, the effects of activation and knockdown of SIRT1 or its downstream target molecules in syncytialized BeWo cells were evaluated. ResultsSIRT1 was expressed by syncytiotrophoblast across normal gestation. In preeclamptic premature aging placentas, SIRT1 was significantly downregulated, while senescence- and extracellular matrix (ECM) -related protein levels were upregulated compared to controls. Immunohistochemistry showed these changes to be confined to syncytiotrophoblast. In vitro, SIRT1 activation in response to resveratrol (RSV) abrogated senescence in forskolin-induced syncytialization of BeWo cells via regulation of senescence- and ECM-related proteins, and filamentous actin (F-actin). These effects were restored by SIRT1 siRNA. DiscussionThe downregulation of SIRT1 may accelerate senescence of syncytiotrophoblast via targets contributing to regulation of the cell cycle, ECM production and cytoskeleton reorganization leading to premature placental aging observed in preeclampsia.

Suspecting Neonatal Severe Primary Hyperparathyroidism in Late Onset Neonatal Sepsis

Background: Neonatal severe primary hyperparathyroidism (NSPHPT) is disorder characterized by severe hypercalcemia and severe hyperparathyroidism resulting from a loss of function of the calcium-sensing receptor (CaSR), encoded by a gene located on the long arm of chromosome 3 (3q-13.3-21). It can be fatal if timely management is not initiated. Clinical Description: A 10-day-old exclusively breastfed girl presented with poor feeding, constipation, and lethargy for 2–3 days before admission. She was born of third-degree consanguinity to a primiparous woman with normal gestation. Born at term, with a birth weight of 3.1 kg, she was discharged uneventfully on day 3 of life. At admission, she was hemodynamically stable and normothermic but exhibited tachypnea, dehydrated with 15% weight loss as compared to birth weight, lethargy, and hypotonia. Salient investigations showed euglycemia, no dyselectrolytemia, and negative sepsis screen, but severe hypercalcemia and hyperparathyroidism. A final diagnosis of NSPHPT was made. Clinical exome sequencing showed homozygous CaSR gene frameshift mutation on chromosome 3. Management: Hypercalcemia was managed initially by standard protocol, including furosemide, hyperhydration, bisphosphonates, and cinacalcet. Subsequently, parathyroidectomy was performed at 2 months of age. Postoperatively, the infant is 5 months old and thriving well. Conclusion: NSPHPT should be considered in the presence of features of clinical sepsis, failure to timely regain birth weight, and a profile suggesting atypical calcium homeostasis.

EID1 plays a protective role in early-onset pre-eclampsia via promoting proliferation and invasion in trophoblast cells

Pre-eclampsia is a pregnancy-specific syndrome, which is partly due to abnormal proliferation and invasion of trophoblast cells. EP300 interacting inhibitor of differentiation 1 (EID1) participates in cell proliferation and invasion. This study aims to investigate the roles of EID1 in trophoblast cells and pre-eclampsia. The expression of EID1 in placental tissues from 60 women with pre-eclampsia and 60 health pregnancies was detected by real-time PCR and immunohistochemical staining. EID1 was overexpressed or silenced by transfection of plasmid or siRNA in HTR-8/SVneo trophoblast cells, and then cell proliferation, cell cycle transition, migration, and invasion were determined by CCK-8 assay, flow cytometry, immunofluorescent staining, immunoblotting, and transwell assays. In addition, the activity of Akt/b-catenin signaling was measured by immunofluorescent staining and Western blot. EID1 mRNA level was decreased in placental tissues of pre-eclampsia patients, especially early-onset pre-eclampsia, accompanied by more severe clinical manifestation and a higher rate of fetal growth restriction (FGR). Gain- and loss-of-function experiments demonstrated that EID1 promoted proliferation and cell cycle transition, migration, and invasion in HTR-8/SVneo cells and its knockdown played opposite roles, suggesting that EID1 may be required for normal gestation. Akt/b-catenin signaling was activated after EID1 forced expression and deactivated after its silencing. EID1 promoted proliferation and invasion of cultured trophoblast cells with possible involvement of Akt/b-catenin signaling. These findings may provide novel insights for the diagnosis and treatment of early-onset pre-eclampsia in a clinic.

6 Evaluation of Surgical Transfers Within the Neonatal Intensive Care Unit

Abstract Aim To assess the outcomes of neonates born between 1st March 2013–7th July 2021 transferred out of the NICU at the RUH Bath for surgical investigation. To also undertake a study of neonates transferred with suspected necrotising enterocolitis looking at types of treatment received and long-term health outcomes. Method A retrospective search was undertaken evaluating records on the BadgerNet UK neonatal database. Outcomes following surgical diagnosis were then evaluated using Millennium, looking at discharge summaries, clinic notes and subsequent hospital admissions. Results 93 neonates were identified as being transferred out for surgical investigation. 58% of patients were male (n = 54) and 42% female (n = 39). 70 were found to have at least one surgical diagnosis, with 80 surgical diagnoses identified. 60% were diagnosed with a congenital condition (n = 42). Overall mortality rate was 7.45%. 29 neonates were transferred out with suspected necrotising enterocolitis, 62% male (n = 18) and 38% female (n = 11). Average age at time of surgical transfer was 22 days. 48.3% were confirmed to have NEC (n = 14), 24% given an alternative diagnosis (n = 7) and 27.6% found to have normal investigation findings (n = 8). Average gestation of neonates with confirmed NEC was 30+0 weeks, average birthweight 1368g (3lb). Conclusions There are a broad range of surgical conditions amongst infants during the neonatal period, many associated with high levels of morbidity and mortality if left untreated. It is important to identify suspected surgical conditions as soon as possible through thorough assessment and multi-disciplinary team management amongst neonatologists, paediatricians, surgeons, and transfer teams; this ensures good prognostic outcomes.

Pregnancy and neonatal outcomes after periconceptional exposure to isotretinoin in Koreans.

ObjectiveIsotretinoin should not be used during pregnancy because of the risk of birth defects. Most pregnant women exposed to isotretinoin choose voluntary pregnancy termination due to concerns about birth defects. However, birth outcome data supporting the termination of pregnancy are lacking. This study aimed to evaluate pregnancy and neonatal outcomes after periconception exposure to isotretinoin.MethodsThis was a prospective cohort study. We evaluated pregnancy and neonatal outcomes after exposure to isotretinoin in 151 pregnant women. Among 1,026 callers at the Korean Teratology Information Service from 2001 to 2017 exposed to isotretinoin during the periconception period, 151 pregnant women who received counseling on teratogenic risk after visiting the clinic were included.ResultsAmong the 151 participants who visited the clinic, only 42 were evaluated using ultrasonography until approximately 20 weeks of gestation. Ultimately, 23 patients were included in the study. The average gestation period during the last exposure to the drug was 2 weeks, and the average daily exposure dose was 12 mg. There were two cases of major birth defects in the exposure group. Spontaneous abortion rates were 17.7% and 8.7% in the exposure and non-exposure groups, respectively (P=0.035). There was no significant difference between the exposure and non-exposure groups in terms of pregnancy and neonatal outcomes.ConclusionThere was no significant difference in pregnancy and neonatal outcomes, including birth defects, between the exposure and non-exposure groups. Further studies with larger sample sizes are required to validate our findings.

Proteome-defined changes in cellular pathways for decidua and trophoblast tissues associated with location and viability of early-stage pregnancy

BackgroundIn early pregnancy, differentiating between a normal intrauterine pregnancy (IUP) and abnormal gestations including early pregnancy loss (EPL) or ectopic pregnancy (EP) is a major clinical challenge when ultrasound is not yet diagnostic. Clinical treatments for these outcomes are drastically different making early, accurate diagnosis imperative. Hence, a greater understanding of the biological mechanisms involved in these early pregnancy complications could lead to new molecular diagnostics.MethodsTrophoblast and endometrial tissue was collected from consenting women having an IUP (n = 4), EPL (n = 4), or EP (n = 2). Samples were analyzed by LC–MS/MS followed by a label-free proteomics analysis in an exploratory study. For each tissue type, pairwise comparisons of different pregnancy outcomes (EPL vs. IUP and EP vs. IUP) were performed, and protein changes having a fold change ≥ 3 and a Student’s t-test p-value ≤ 0.05 were defined as significant. Pathway and network classification tools were used to group significantly changing proteins based on their functional similarities.ResultsA total of 4792 and 4757 proteins were identified in decidua and trophoblast proteomes. For decidua, 125 protein levels (2.6% of the proteome) were significantly different between EP and IUP, whereas EPL and IUP decidua were more similar with only 68 (1.4%) differences. For trophoblasts, there were 66 (1.4%) differences between EPL and IUP. However, the largest group of 344 differences (7.2%) was observed between EP and IUP trophoblasts. In both tissues, proteins associated with ECM remodeling, cell adhesion and metabolic pathways showed decreases in EP specimens compared with IUP and EPL. In trophoblasts, EP showed elevation of inflammatory and immune response pathways.ConclusionsOverall, differences between an EP and IUP are greater than the changes observed when comparing ongoing IUP and nonviable intrauterine pregnancies (EPL) in both decidua and trophoblast proteomes. Furthermore, differences between EP and IUP were much higher in the trophoblast than in the decidua. This observation is true for the total number of protein changes as well as the extent of changes in upstream regulators and related pathways. This suggests that biomarkers and mechanisms of trophoblast function may be the best predictors of early pregnancy location and viability.

Gestational Insulin Resistance Is Mediated by the Gut Microbiome–Indoleamine 2,3-Dioxygenase Axis

Normal gestation involves a reprogramming of the maternal gut microbiome (GM) that contributes to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of the GM-maternal metabolism interaction. The GM and plasma metabolome of CD1, NIH-Swiss, and C57 mice were analyzed with the use of 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry throughout gestation. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM was studied with the use of fecal microbial transplants (FMTs). Significant variation in GM alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time point specific, with the species enriched at gestation day 15/19 (G15/19), a point of heightened IR, being distinct from those enriched before or after pregnancy. Metabolomics revealed elevated plasma kynurenine at G15/19 in all 3 mouse strains. IDO1, the rate-limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine level effects on IR derive from the GM in both mouse and human pregnancy. GM changes accompanying pregnancy shift IDO1-dependent tryptophan metabolism toward kynurenine production, intestinal inflammation, and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1. (Gestational Gut Microbiome-IDO1 Axis Mediates Pregnancy Insulin Resistance; EMBL-ENA ID: PRJEB45047. MetaboLights ID: MTBLS3598).

Ранние дезадаптивные схемы и тип отношения к беременности у женщин на позднем сроке гестации

<p style="text-align: justify;">The work is aimed at studying the early maladaptive schemes of women and the type of attitude to pregnancy at late gestation. The materials of an empirical study obtained on a sample of women in late pregnancy are presented. The average gestation period was 38.9±0.92 weeks. The study involved 122 women aged 18 to 40 years (mean age — 28.84±6.1 years). The design of the study included a method for diagnosing Jeffrey Young's Early Maladaptive Schemes (YSQ-S3R, adapted by P.M. Kasyanik, E.V. Romanova (2013)), the test of the relationship of a pregnant I.V. Dobryakova (E.G. Eidemiller, I.V. Dobryakov, I.M. Nikolskaya, 2003). The following results were obtained: significant differences in the types of psychological components of gestational dominance in women, depending on age, were revealed. For women aged 26-30 years, to a greater extent than for women under 25 years, the optimal type of psychological component of the gestational dominant is typical (p=0.05). The highest values were obtained for the domain "Broken boundaries". The domains "Communication disruption and rejection" and "Impaired autonomy" are the least pronounced in women in late pregnancy. For women with an optimal type of attitude to pregnancy, the early maladaptive scheme of "Social alienation" is less characteristic. For women with a euphoric type of attitude to pregnancy, such early maladaptive schemes as "Self-sacrifice", "Strict standards / Pickiness", and "Seeking approval" are more typical. Two reliable regression models were obtained and described for the euphoric type of attitude to pregnancy (F=1.77, R<sup>2</sup>=0.236, p=0.039) and the optimal type (F=2.19, R<sup>2</sup>=0.277, p=0.007). As possible predictors of the euphoric type of attitude to pregnancy and childbirth, we can distinguish the following: a) a lack of expectation from others of deception and manipulation; b) a lack of need to control their emotions, and c) increased demands on others, as possible predictors of the optimal type of attitude to pregnancy a) a need for cohesion, connectivity with others; b) attention to their needs and unwillingness to sacrifice them "at the behest" of others; c) an increased need to control their emotions and impulses and d) confidence that they have a special social status and privileges.</p>

Pediatric patient with oculocutaneous albinism

Oculocutaneous albinism (OCA) is a heterogeneous autosomal recessive disorder characterized by a reduced or absent melanin synthesis. OCA causes a complete or partial absence of pigment in the skin, hair, and eyes. Reduction of melanin in the eyes results in reduced visual acuity, photophobia, and nystagmus. A 6-year-old boy, the first child of a related couple, was born following a normal gestation and delivery. At term, he weighed 3800 g, and his length was 50 cm. OCA was noted at birth; there was total depigmentation of the skin, hair, and iris. He presented with photophobia and bilateral strabismus. The patient had white hair, eyebrows, eyelashes, and depigmented skin (A). Ophthalmologic examination revealed characteristic iris depigmentation and translucency (B), retinal depigmentation (C), misrouting of the optic nerve fibers and reduced visual acuity (5/10). He had a normal mental development with no other congenital deformities. He did not have any abnormalities of the internal organs. The diagnosis of OCA is based on clinical findings of hypopigmentation of the skin and hair, in addition to the characteristic ocular symptoms. However, due to the clinical overlap between the OCA subtypes, molecular diagnosis is necessary in order to establish the gene defect and thus the OCA subtype. Reduced visual acuity can be helped in various ways. Glasses, possibly bifocals, may often be of sufficient help. Oculocutaneous albinism is an autosomal recessive disorder that presents with heterogeneous expressivity.

Is perinatal asphyxia associated with an increase in serum bilirubin in neonates? A case-control study.

Perinatal asphyxia affects different organs of body depending upon the severity of hypoxemia and ischemia. This study was carried out to evaluate severity of hyperbilirubinemia in relation to severity of asphyxia. A case-control study. Asphyxiated newborns with Apgar score ≤7 at 1 min. and categorized as severe birth asphyxia according to the WHO classification of diseases (ICD10) were matched with controls without birth asphyxia. All babies were examined twice daily for dermal icterus until start of phototherapy. Babies with congenital heart disease, sepsis, cephalohematoma, blood group incompatibility were excluded. Arterial blood gas analysis was done along with serial TSB measurement as per standard guidelines. 50 cases and 50 matched controls were enrolled. The average birth weight and gestation in cases was 2427 ± 30.05 g and 35.9 ± 2.5 weeks and among control it was 2633 ± 378.62 g and 37.76 ± 0.116 weeks. Among cases, onset of jaundice was 56.64 ± 20.43 h compared to 63.36 ± 23 h in control group. In the cases, the average pH was 7.31 ± 0.06, CO2 was 41.52 ± 84, O2 was 94.98 ± 14.83, and HCO3 was 18.56 ± 2.04. The rise and peak of serum bilirubin differed between the case and control groups; in the cases, the peak occurred at the 22nd h of life, then plateaued from the 40th to the 78th hour of life, and ultimately fell at the 96th hour of life. In comparison, the rise and peak of serum bilirubin occurred comparatively late in the control group. The rise and peak in the control group occurred at the 80th and 96th h of life, respectively. The multiple linear regression analysis showed CRP, Apgar at 5 min. below 7 and male gender significantly affects the rise of serum bilirubin (P < 0.05). The peak serum bilirubin in asphyxiated newborns occurs earlier, and plateau for longer duration compared to normal newborns. Low Apgar at 5 min. has significant correlation to earlier rise of bilirubin.

Life-history traits and fitness of plateau pika (Ochotona curzoniae) in alpine meadow ecosystem.

Plateau pika (Ochotona curzoniae) is an endemic mammal living in the alpine meadow ecosystem in Qinghai–Tibet Plateau. We studied life history of plateau pika by mark–recapturing method. The research results showed that fitness of plateau pika to its habitat was lower than those of many other mammal species; plateau pika adopted quick growth strategy; the life‐history features of plateau pika were accorded with Charnov (Evolutionary Ecology Research, 2002, 4, 749)'s formula about life‐history classification, that is, E/α ≈ 1.35, C·E ≈ 1.7, I/m ≈ 0.3, in which E stands for average adult life span; α stands for age at first reproduction; C is reproductive effort; I is the size of an offspring at independence from the parent; m is average adult body mass. There does not exist dimorphism in plateau pikas. The configurations of females and males are similar; the average body mass of males is a little heavier than that of females, but the difference is not significant (F = 1.0854, df = 154, p > .3058). The juveniles exhibit a J‐form growth curve before 30‐day age and grow slower between 30 and 65‐day age and reach body mass equilibrium at about 65 days old. So, 65 days is the maturity age of plateau pika. There are 3 mortality peaks in plateau pika population. The first time is in neonate period, when only one half of juveniles can pass through this period, which implies that juvenile period is influenced strongly by natural selection; the second time is in fecundity peak period, which reflects the cost of reproduction; the third time is in the old age of plateau pika, a significant loss occurs during this period, which is the result of natural selection. The average longevity of females is longer than that of males. A female reaches the maximum life span recorded, that is, 931 days. The average longevity of all individuals is 16.33 months ≈ 490 days. The survival rate of females is higher than that of males, which reflects the cost of reproduction and society role of males. It is the outcome of natural selection. The sex ratio of neonates is 1:1; however, the sex ratio of adults is female: male = 1.31:1, which is caused by higher mortality of males over females in life history. Plateau pikas reproduced two times every year. The average gestation period of females is 18–20 days. The average litter size is 4.57 individual. The average body mass of neonates is 9.28 g. The average litter size of adult female plateau pika does not variate with age. Breeding season is between April and June. The reproductive value and fertility of 15–18 months age females are highest. The reproductive value and fertility increased with age before reproductive value and fertility peak age; however, the reproductive value and fertility decreased with age after peak age. The fitness of plateau pika (r = .1125) was lower than that of American pikas (O. princeps) (r = 2.172). The survival rate was the main factor influencing fitness. The dynamic trend of plateau pika population was coincident with r, that is, the plateau pika population was stable.

Umbilical Vein Pulse Wave Spectral Analysis: A Possible Method for Placental Assessment Through Evaluation of Maternal and Fetal Flow Components.

Placental blood flow analysis is complicated by having both maternal and fetal flow components. Using the Fast Fourier Transform (FFT) of the umbilical venous pulse wave spectra (PW) envelope, we could simultaneously assess maternal/fetal blood flow in the placenta and investigate if normal and intrauterine growth restriction (IUGR)/pre-eclamptic pregnancies could be distinguished. This retrospective study included normal gestations (N=11) and gestations with IUGR, pre-eclampsia, or both (N=13). Umbilical vein PW were acquired and spectral envelopes were identified as a function of time and analyzed by FFT. Base-10 logarithms of the ratios of the maternal/fetal spectral peaks (LRSP) were compared in normal and IUGR/pre-eclamptic populations (two-tailed t-test). Body mass index (BMI), gestational age at scan time, placental position, and weight-normalized umbilical vein blood volume flow (two-tailed t-test, analysis of variance [ANOVA] analysis) were tested. P < .05 was considered significant. The LRSP for normal and IUGR/pre-eclamptic pregnancies were 0.141 ± 0.180 and -0.072 ± 0.262 (mean ± standard deviation), respectively (P=.033). We detected differences between normal gestations and combinations of LRSP and weight-normalized umbilical venous blood flows. Placental effects based on LRSPs and blood flow may act synergistically in cases with both pre-eclampsia and IUGR (P=.014). No other significant associations were seen. In this preliminary study, we showed that umbilical venous flow contains markers related to placental maternal/fetal blood flow, which can be used to assess IUGR and pre-eclampsia. When coupled with umbilical cord blood flow, this new marker may potentially identify the primary causes of the two conditions.