Evaluation of prenatal diagnosis of cleft lip/palate by foetal ultrasonographic examination

Ultrasound scans in the midtrimester of pregnancy are now a routine part of antenatal care in many countries. This type of screening procedure can detect serious foetal anomalies. Thanks to our registry of congenital anomalies a study was undertaken. The objective of the study was to evaluate prenatal detection of cleft lip (palate)(CL/P) by routine ultrasonographic examination of the foetus in 265679 consecutive pregnancies from 1979 to 1998. The percentage of prenatal detection of CL/P was low. For isolated malformation (foetuses with only CL/P) the detection rate was low: 17.8%; however, this detection rate increased from 5.3% during the period 1979-1988 to 26.5% during the period 1989-1998, for foetuses with associated malformations (foetuses with CL/P and one or more additional major malformations) these detection rates were 34.6, 13. 3 and 50.0%, respectively. In foetuses with associated malformations with CL/P this detection rate was higher for chromosomal abnormalities with CL/P and for non-syndromic, non-chromosomal multiply malformed children with CL/P than for non-chromosomal recognized syndromes with CL/P.     

Pathogenic copy number variations are associated with foetal short femur length in a tertiary referral centre study

Shortened foetal femur length (FL) is a common abnormal phenotype that often causes anxiety in pregnant women, and standard clinical treatments remain unavailable. We investigated the clinical characteristics, genetic aetiology and obstetric pregnancy outcomes of foetuses with short FL and provided a reference for perinatal management of such cases. Chromosomal microarray analysis was used to analyse the copy number variations (CNV) in short FL foetuses. Of the 218 foetuses with short FL, 33 foetuses exhibited abnormal CNVs, including 19 with pathogenic CNVs and 14 with variations of uncertain clinical significance. Of the 19 foetuses with pathogenic CNVs, four had aneuploidy, 14 had deletions/duplications, and one had pathogenic uniparental diploidy. The 7q11.23 microdeletion was detected in three foetuses. The severity of short FL was not associated with the rate of pathogenic CNVs. The duration of short FL for the intrauterine ultrasound phenotype in foetuses carrying a pathogenic CNV was independent of the gestational age. Further, maternal age was not associated with the incidence of foetal pathogenic CNVs. Adverse pregnancy outcomes occurred in 77 cases, including termination of pregnancy in 63 cases, postnatal dwarfed foetuses with intellectual disability in 11 cases, and three deaths within 3 months of birth. Pathogenic CNVs closely related to foetal short FL were identified, among which the 7q11.23 microdeletion was highly associated with short FL development. This study provides a reference for the perinatal management of foetuses with short FL.     

Prenatal diagnosis of Pallister-Killian syndrome and literature review

Pallister-Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2−4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS.     

Cervical cancer in pregnancy: Analysis of the literature and innovative approaches

Cervical cancer is one of the most common gynecological malignancies diagnosed during pregnancy although, fortunately, it is a rare event. In majority of cases, the management of cervical cancer in pregnant women is not different from nonpregnant women and prognosis seems not compromised by pregnancy. The association between cancer and pregnancy appears to be a significant challenge for women and specialists and the decisions about therapy must be individualized and taken by a multidisciplinary team. This review is focused on cervical cancer in pregnancy. The aim is to discuss the diagnosis, potential biomarkers and molecular aspects, therapeutic approaches, and prognosis from intraepithelial cervical neoplasia to invasive cervical cancer (early and advanced stages) in different gestational ages. We provide an overview of the current literature regarding the treatment strategies of concurrent pregnancy and cervical cancer cases and we propose some clinical advices to help clinicians to manage this condition. A mention about the effects of the conservative therapy (as conization) on fertility, the human papillomavirus vaccine in pregnant women and our center's experience with obstetrical and oncological outcomes are reported.     

择期经阴道宫颈环扎术与期待疗法治疗宫颈机能不全的效果比较

目的:比较择期经阴道宫颈环扎术以及期待疗法治疗宫颈机能不全的效果。方法:选择2017年10月~2019年10月我院收治的201例宫颈机能不全患者,将其随机分为两组。对照组100例患者采取期待疗法,即卧床休息,口服地屈孕酮,每次服用的剂量为10 mg,每日2次,一直服药到30孕周;观察组101例患者择期经阴道宫颈环扎术,比较两组的早产率、成功妊娠率、新生儿出生体重以及分娩孕周。结果:对照组100例宫颈机能不全患者中,22例患者流产(占22.00%),78例患者获得活婴(占78.00%),78例成功分娩的患者中,47例患者≥37周分娩,31例患者<37周分娩,早产率为39.74%(31/78)。观察组的101例患者中,8例患者流产(占7.92%),93例患者获得活婴(占92.08%)。93例成功分娩的患者中,81例患者≥37周分娩,12例患者<37周分娩,早产率为12.90%(12/93);12例早产的患者中,4例患者由于胎膜早破和胎儿窘迫,而在孕32~33周采取剖宫产手术,2例患者由于胎膜早破臀位,而在孕35~36周时采取剖宫产手术,6例患者在孕35~36周早产。观察组宫颈机能不全患者的早产率明显低于对照组(P<0.05),且成功妊娠率、新生儿出生体重以及分娩孕周明显高于或长于对照组(P<0.05)。结论:与期待疗法相比较,择期经阴道宫颈环扎术不但可以明显延长宫颈机能不全患者的分娩孕周,提高成功妊娠率,还能改善新生儿的预后、降低早产的风险。     

Neonatal complications in infants born to mothers with diabetes mellitus

Health status of 53 babies delivered by diabetic mothers are discussed. Neonatal period was uncomplicated only in 12 cases. The remaining babies suffered from respiratory disorders, edema, neurological disturbances, prolonged jaundice, infections etc. Metabolic disorders in diabetic female are unfavourable for the development of pregnancy and neonate health. it may be improved by the proper diagnostico-therapeutical management prior to and during pregnancy and by intensive care of neonates after delivery. It requires, however, the establishment of health institution with highly qualified teams well equipped which will be able to carry out diagnosis and therapy of diabetes mellitus in females in the reproductive age, during pregnancy as well as proper care of the neonates.     

Herniation of gravid uterus: report of 2 cases and review of literature

Anterior abdominal wall hernias are uncommon, and herniation of a gravid uterus into these hernias is even rarer. Although reducible initially, the herniation of pregnant uterus may be complicated by incarceration and subsequent strangulation within the hernial sac, late in the course of pregnancy. There is no consensus over the management of this rare condition. Each case should be individualized. If uncomplicated, a conservative approach until term followed by delivery and herniorrhaphy is a good option. Here, 2 cases of herniation of gravid uterus into the anterior abdominal wall are described along with a brief review of literature pertaining to its presentation, complications, and management.     

Microstructural observations of villous and membrane histology in monochorionic triplet placenta after in vitro fertilization

The frequency of triplet gestation is low in humans, estimated at 1:6400 deliveries. Monochorionic gestations represent a subpopulation of approximately 10% of these triplet pregnancies. Hypertensive complications are known to occur with greater frequency in the context of multiple gestation. In this report we describe microscopic placental changes associated with pre-eclampsia and proteinuria in the setting of an uncommon monochorionic-triamniotic triplet pregnancy achieved via in vitro fertilization. Histologic features observed in this case include placental stromal fibrosis and increased syncytial nodularity (Tenney-Parker change). In this triplet delivery resulting from two consecutive fissions of a single embryo, chorion and amnion configuration are also characterized with a review of the literature discussing the potential relationship between in vitro culture conditions and monozygotic multiple gestation.     

生物蛋白胶封堵合并宫颈环扎术治疗胎膜早破的疗效观察

目的:观察生物蛋白胶封堵合并宫颈环扎术治疗胎膜早破,对孕妇、胎儿及新生儿的影响,明确该技术治疗胎膜早破的疗效。方法:我院产科共收治妊娠<30周胎膜早破患者48例,采用生物蛋白胶封堵合并宫颈环扎术治疗胎膜早破,观察治疗后孕妇羊水指数,胎儿双顶径,新生儿出生时体重,及孕妇的副反应。结果:在本次封堵治疗过程中均一次封堵成功,没有不良反应发生,所有孕妇术后阴道流水情况均明显改善,其中有2例孕妇术后1周阴道流水停止。所有孕妇术后羊水漏出量均明显减少,B超检查显示羊水指数均在(6±2)cm,胎儿每周双顶径增长均达到(0.15±0.02)cm,延长孕周最短(5±2)w,10例早产,38例继续妊娠至37 w。新生儿出生时体重为(2000±260)g,无1例发生NRDS。同期没有进行宫颈内封堵仅行药物保胎治疗的10例孕妇,胎龄延长最长达到10 d,最短者24 h内出现早产分娩,早产儿平均体重1400 g,均发生NRDS,有2例放弃治疗,4例在NICU行治疗,最终因各种并发症死亡。48例行封堵治疗孕妇未发生过敏反应,无阴道出血及产后出血和感染等。结论:应用生物蛋白胶结合宫颈环扎术治疗胎膜早破,手术操作简单,可延长了孕周,提高了新生儿成活率,无不良反应,具有广泛的应用前景。     

Manipulation of cytokine production profiles as a therapeutic approach for immunologic pregnancy loss

Pregnancy is not as successful as one might think; it can be compromised by several complications such as recurrent spontaneous miscarriage, pre-term delivery, pre-eclampsia etc. Much attention has been paid to the possibility of the maternal immune system mediating deleterious effects on pregnancy. Research conducted during the last two decades has shed much light on cell-mediated immunologic effectors that might underlie these pregnancy complications. Of particular interest are the effects that pro-inflammatory and anti-inflammatory cytokines have on the foetus and placenta, and thus on the success and failure of pregnancy. This review presents evidences that certain cytokine profiles are associated with recurrent miscarriage and pre-term delivery and discusses possible pathways of effector function of cytokines in pregnancy loss and the redirection of cytokine profiles from one that is antagonistic to pregnancy towards one that is conducive to the success of pregnancy. Among the promising agents for the modulation of the Th1/Th2 balance are progestogens like progesterone and dydrogesterone; this review also discusses recent evidence that progestogens are capable of modulating cytokine production patterns in pregnancy loss.     

Routine cervical cerclage in higher order multiple gestation -- does it prolong the pregnancy?

Preterm birth following cervical dilatation is the greatest threat to infants of a multiple pregnancy. Lacking reliable data concerning the effect of prophylactic cerclage, we compared a study group to controls for maternal and perinatal outcome. Sixteen of 94 triplet-, 9 of 18 quadruplet/quintuplet-pregnancies, treated with prophylactic cerclage, were retrospectively compared to those without cervical cerclage respectively. Kruskal-Wallis test and Mann-Whitney-U test were performed as non-parametric one way analysis of variance. For the analysis of frequencies Chi Square test or Fisher's exact test were performed. Odds ratio with 95% confidence interval was used to compare the need for intravenous tocolysis as well as perinatal morbidity and mortality. Gestational age at delivery was not different from the controls in all studied groups. Birth weight revealed a 200 g dominance for the "no cerclage-triplets", while this significant difference was inverted for quadruplets/quintuplets (1245 g vs. 1069 g). With respect to gestational age at birth, need for hospitalisation or medical intervention no benefit was achieved. Moreover, perinatal outcome analysed by arterial pH, APGAR-Score and perinatal mortality was not altered by a prophylactic cerclage. Perinatal morbidity for quadruplets and quintuplets was even higher in cerclage pregnancies. Therefore, these retrospective results disclaim a positive impact of cervical cerclage on pregnancy management or perinatal outcome in multifetal pregnancies.     

Prenatally diagnosed foetal malformations and termination of pregnancy: the case of Lebanon

Termination of pregnancy (TOP) is offered in many countries, for foetuses prenatally diagnosed with congenital malformations that are deemed incompatible with life or that are associated with a high morbidity. In Lebanon, a middle income country where religion plays a focal role, the law prohibits any form of TOP unless it is the only means to save the mother's life. It is the contention of the authors of this article that even if the foetus is a person, if it were medically revealed that there is a substantial risk that the newborn will suffer severe physical abnormalities that will cause it to be seriously handicapped; it is morally acceptable to terminate the pregnancy. Hence, TOP carried out for these indications is justified in the interest of the foetus and the child. Whatever the status of the foetus is, once born, it will become a full-fledged sentient being with all that this entails. When given the option of starting an existence, this person-to-be has the right to a minimum that allows him/her to enjoy a relatively good quality of life. Today, Lebanese obstetricians are confronted with the burden placed on them under the law to refuse TOP, or, when performing them, to forge records or deny having done them. This is why we strongly believe that the Lebanese policy on abortion should be amended.     

Endoglin (CD105) immuno-expression in human foetal and neonatal lungs

Endoglin is a 180 KDa glycoprotein mainly expressed on endothelial cells of newly formed vessels. Its expression is increased by the hypoxia inducible factor 1 (HIF-1), a potent stimulator of VEGF expression. The relative hypoxic environment in which foetal lung develops favours HIF-1 dependent gene expression, including the endoglin and VEGF ones. Herein, we analysed endoglin immunoexpression in the human neonatal and foetal lung throughout gestation. Lungs from 18 foetuses (9-41 weeks), 7 preterm and 2 term infants were submitted to the immunohistochemical study. A slight immunostaining was found in some mesenchymal aggregates in the lungs of foetuses at the first trimester of pregnancy. At mid gestation, endoglin was evidenced in peri-tubular mesenchymal stem cells or in peri-canalicular vessels and in the endothelia of peri-bronchial vessels; by contrast, no immunoreaction was observed in case of Down syndrome or in a foetus with cardiac malformations. At late gestation and in preterm infants, endoglin antibody labelled endothelia of the alveolar capillaries and of peri-bronchial vessels. In case of alveolar capillary dysplasia (ACD) or macrosomy associated with maternal diabetes, endoglin expression was restricted to peri-bronchial vessels; no immunoreaction was encountered in foetuses with IUGR (intra-uterine growth restriction) or massive pulmonary haemorrhage. Lungs of term infants both displayed atelectasis; there was no evidence of endoglin immunoexpression in one case, whereby only the endothelia of peri-bronchial vessels were stained in the other. Our study suggests that lung vasculogenesis endures throughout gestation. Absence of endoglin staining in some pathologic conditions may reflect lung vasculogenesis disorders; nonetheless, since each pathologic state is represented by a single case in our cohort, further studies are required to clarify this issue.     

救援性宫颈托治疗紧急宫颈环扎术后再次宫颈缩短和/或宫口扩张的临床观察

摘要 目的：观察救援性宫颈托治疗在治疗紧急宫颈环扎术后发生进一步宫颈缩短和/或宫口开大患者的临床结局。方法：2021年05月31日至2022年01月13日于哈尔滨医科大学附属第一医院产科行紧急宫颈环扎术的患者,术后超声监测宫颈长度、内诊,对于超声提示宫颈缩短和/或宫口扩张,经阴道检查可见宫颈管扩张伴胎胞暴露的患者（单胎）进行救援性宫颈托治疗（11例）。随访观察其妊娠结局及不良反应。结果：进行紧急宫颈环扎术孕周为107-201天（平均165.5±34.9天）;救援性宫颈托放置孕周为169-262天（平均205.9±26.1）;分娩孕周为193-269天（平均249.5±24.9天）;延长天数为18-160天（平均84.0±46.3天）。未出现医源性胎膜早破及绒毛膜羊膜炎。11例患者中10例患者获得新生儿。存活的10例新生儿4例于新生儿科住院治疗,均后期顺利出院,新生儿存活率为100%。结论：本组病例使用救援性宫颈托明显延长紧急宫颈环扎术后宫颈缩短和/或宫口扩张患者的孕周,改善妊娠结局。     

Plasma Testosterone in Cows Related to Day of Gestation and Sex of the Foetus,and Plasma Testosterone Levels Around Parturition

No significant differences in plasma testosterone level were observed between cows carrying a male foetus and cows carrying a female foetus at any ten-day interval from day 35 of gestation until parturition. Reported higher abortion rates for male than for female foetuses would thus appear not to be due to effects of foetal testosterone on the maternal endocrine balance. In spite of a great individual variation in plasma testosterone values at similar stages of gestation, certain trends are evident. From the 35th to the 80th day of gestation the average concentration was 90–100 pg/ml. Later it rose and reached 200 pg/ml on the 180th day, remaining at this level until after partus. During the first day after parturition plasma testosterone fell significantly and stabilized around 120 pg/ml.     

Uterine blood flow in sows: effects of pregnancy stage and litter size

Female pigs were assigned to three groups at 94 days of age: a control group (CTR), a group undergoing the ligation and severing of the left oviduct (LIG), and a group undergoing right hysteroovariectomy (HHO). They were inseminated at 307 days of age. At 35 days of pregnancy, an ultrasonic transit time flow probe was implanted around the middle artery of one uterine horn in 33 sows and uterine blood flow was measured during thirteen 24-h periods between 44 and 111 days. Despite large differences in ovulation rate per uterine horn (4.8, 8.3 and 16.9 in the LIG, CTR and HHO groups, respectively), variation of litter size was considerably reduced with advancement of pregnancy (3.0, 6.6 and 10.8 foetuses per uterine horn at 35 days, and 3.0, 5.8 and 4.9 at 112 days (slaughter), respectively). Uterine blood flow increased linearly during pregnancy. It was lower in the LIG sows (0.82 to 1.74 L x min(-1) x horn(-1) from 44 to 111 days) than in the CTR and HHO sows (1.22 to 2.84 and 1.09 to 2.63 L x min(-1) x horn(1), respectively). It was more closely related to litter weight than to litter size and amounted to 0.42 L x min(-1) x kg foetus(-1) at 111 days. Uterine blood flow per foetus decreased when litter size increased. It increased from 0.31 to 0.72, 0.26 to 0.60 and 0.20 to 0.43 L x min(-1) x foetus(-1) from 44 to 111 days when there were 2 to 3, 4 to 5, and 6 to 8 foetuses in the uterine horn, respectively. This explains why piglets from large litters are lighter at birth.     

Cardiac surgery and percutaneous intervention in pregnant women with heart disease

In pregnant women with heart disease, complications can arise due to the haemodynamic burden of pregnancy and to hypercoagulation. Most problems can be managed medically, but sometimes cardiac surgery or percutaneous intervention is unavoidable. Cardiac surgery has similar maternal mortality to that outside pregnancy, but foetal mortality and morbidity are considerable. Measures to reduce the risk by adaptation of the management of cardiopulmonary bypass are described. When gestational age is > 28 weeks, pre-surgery delivery of the foetus should be considered. Percutaneous intervention exposes the foetus to radiation. The radiation dose for common cardiac procedures, however, does not result in detectable harmful foetal effects.     

Up regulation of the maternal immune response in the placenta of cattle naturally infected with Neospora caninum

Neospora caninum is an intracellular protozoan parasite which is a major cause of abortion in cattle worldwide. It forms persistent infections which recrudesce during pregnancy leading to foetal infection and in a proportion of cases, abortion. The mechanisms underlying abortion are not understood. In this study, recrudescence of a persistent infection in eight naturally infected cows occurred between 20 and 33 weeks of gestation. Animals were killed at the time of recrudescence and parasites were detected in the placentae and foetuses. An active maternal immune response consisting of an infiltration of CD4+ and CD8+ T cells and a 46-49 fold increase in interferon-γ and interleukin-4 mRNA was detected. Other cytokines, notably interleukin-12 p40, interleukin-10 and tumour necrosis factor-α were also significantly increased and Major Histocompatibility Class II antigen was expressed on maternal and foetal epithelial and stromal fibroblastoid cells. Significantly, despite the presence of an active maternal immune response in the placenta, all the foetuses were alive at the time of maternal euthanasia. There was evidence of parasites within foetal tissues; their distribution was restricted to the central nervous system and skeletal muscle and their presence was associated with tissue necrosis and a non-suppurative inflammatory response involving lymphocytes and macrophages, irrespective of the gestational age of the foetus. Whilst an active maternal immune response to a pathogen in the placenta is generally considered to be damaging to the foetal trophoblast, our findings suggest that the presence of a parasite-induced maternal immune response in the placenta is not detrimental to foetal survival but may contribute to the control of placental parasitosis.     

Changes in protein turnover during gestation in the foetuses,placentas, liver,muscle and whole body of rats given a low-protein diet

(1)Protein synthesis and content have been studied in skeletal muscle, liver, foetuses and placentas of pregnant rats given a protein-deficient diet. Changes which occurred during the anabolic and subsequent catabolic phases of pregnancy are compared with those in well-fed pregnant and in protein-deficient non-pregnant rats. (2) The normal increase in liver protein did not occur during pregnancy in the protein-deficient group. (3) Protein deficiency affected protein content of the placenta earlier and more severely than that of the foetus. (4) Rates of protein synthesis in liver, placentas and foetuses were enhanced above control values by protein deficiency. (5)_Muscle protein increased normally during the anabolic phase of pregnancy but fell during the catabolic phase, unlike values for weel-fed animals. (6) Muscle protein synthesis rates rose by similar amounts in well-fed and protein-deficient animals during the anabolic phase of pregnancy. The fall to starting values during the catabolic phase was sharper and earlier in protein-deficient animals, which could reduce demands on the body amino acid pool by an amount equivalent to over 50% of the needs for protein deposition in foetuses and placentas. Thus, changes in muscle protein synthesis in both anabolic and catabolic phases of pregnancy may afford some protection to foetal protein synthesis.     

Prolonged pregnancy: the management debate.

A prospective trial was conducted to compare the effects of conservative management of prolonged pregnancy (conservative group) with routine induction of labour at 42 weeks'' gestation (active group) in otherwise uncomplicated pregnancies. Of the 402 pregnancies studied, 207 (51%) were allocated to conservative management and 195 (49%) were allocated to have labour induced. The groups were well matched for age, parity, and smoking habits. One hundred and sixty six (80%) of the patients in the conservative group went into spontaneous labour. Of the remainder, two underwent elective caesarean section, 19 had labour induced because of clinical concern, and the remaining 20 had labour induced at the patient''s own request. One hundred and twenty five (64%) of the patients in the planned active group underwent induction of labour. Of the remaining 70, 49 went into spontaneous labour and 21 (11%) asked that they should not have labour induced. Comparison of the two groups showed no difference in the length of the first stage of labour but a trend towards an increased need for intervention for fetal distress (p less than 0.06) in the active group. There were no differences in the length of the second stage, the need for intervention, or the mode of delivery. In terms of Apgar scores the neonatal outcome was not significantly different between the two groups, but a greater proportion of the babies (15% v 8%) in the active group required intubation. Umbilical cord venous pH estimated in the last 183 consecutive deliveries in the study showed a significantly lower mean value in the active group (p less than 0.05). There was no difference in birth weight between the two groups. Two deaths occurred in the study. There was a stillbirth in the conservative group at 292 days after massive abruption, and one neonatal death in the active group owing to multiple congenital abnormalities. The outcome for mother and baby in patients from both groups who went into spontaneous labour was generally good. The outcome for patients for whom conservative management was planned but induction became necessary was no different from that of patients who underwent planned induction at term. Thus from our results we can find no evidence to support the view that women with normal prolonged pregnancy should undergo routine induction of labour at 42 weeks'' gestation.