Incidence Of Fetal Malformations Research Articles

Efficacy of discontinuing the use of low-dose aspirin at 28 weeks of gestation for preventing preeclampsia.

Low-dose aspirin (LDA) has been shown to reduce the incidence of preeclampsia (PE). Previous studies have focused on the timing of LDA initiation, but no study to date has assessed the timing of LDA discontinuation. This study aimed to evaluate the effect of LDA when LDA is initiated between 12 and 16 weeks of gestation and continued until 28 weeks of gestation. This prospective cohort study with historical controls investigated singleton pregnancies that were at a high risk for PE. High-risk factors were defined as a history of hypertensive disorders of pregnancy, chronic hypertension, diabetes mellitus, autoimmune disease, obesity, and high normal blood pressure in the first trimester. We performed adjustments using propensity score matching (PSM) for each indication of LDA, maternal age, primiparity, and assisted reproductive technology. The primary outcome was the incidence of PE. Secondary outcomes were the incidence of preterm PE, fetal growth restriction (FGR), preterm birth, fetal malformation, and maternal postpartum hemorrhage (PPH). A total of 203 and 543 participants were assigned to the LDA and control group, respectively. After PSM, there was no significant difference in the incidence of PE (22.0% vs. 16.8%; p=0.20), preterm PE (12.0% vs. 13.1%; p=0.76), FGR (7.9% vs. 12.0%; p=0.17), or preterm birth (17.3% vs. 15.7%; p=0.68). There was also no significant increase in maternal PPH or in the incidence of fetal malformations. Discontinuing the use of LDA at 28 weeks of gestation did not result in a lower incidence of PE and FGR.

Periconceptional folate supplementation for the prevention of congenital heart diseases: A review of literatures

Background: Folate is essential for metabolism and development. So, folate metabolism abnormalities are common in infants with some congenital defects. An infant born to mothers with normal folate status has more resistant to congenital heart diseases (CHDs). Evidence on risk factors for developmental defects resulting from drug use before conception and during pregnancy is still very limited. The relationship between folic acid for mothers before and throughout pregnancy and the incidence of fetal malformations and diseases have been recognized. Aims: This article is a rapid review for assessment of the folic acid supplementation as a preventive measure of CHDs during fetal development, and what is already recognized about a policy of this subject, by using systematic review methods to search some of the existing researches. Materials: publications related to determining and quantifying the use of folate by pregnant mothers to decrease the risk of congenital heart diseases were reviewed. Many studies have confirmed the reduction of congenital heart diseases by folic acid supplementation prior to pregnancy. Conclusion: the protective effect of folic acid against congenital heart abnormalities has been established. Though, the dose and time of supplementation are not known; more researches are needed to explain the mechanisms.

Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice

The use of first and second generation antiepileptic drugs during pregnancy doubles the risk of major congenital malformations and other teratogenic defects. Lacosamide (LCM) is a third-generation antiepileptic drug that interacts with collapsing response mediator protein 2, a protein that has been associated with neurodevelopmental diseases like schizophrenia. The aim of this study was to test the potential teratogenic effects of LCM on developing embryos and its effects on behavioural/histological alterations in adult mice. We administered LCM to pregnant mice, assessing its presence, and that of related compounds, in the mothers’ serum and in embryonic tissues using liquid chromatography coupled to quadrupole/time of flight mass spectrometry detection. Embryo morphology was evaluated, and immunohistochemistry was performed on adult offspring. Behavioural studies were carried out during the first two postnatal weeks and on adult mice. We found a high incidence of embryonic lethality and malformations in mice exposed to LCM during embryonic development. Neonatal mice born to dams treated with LCM during gestation displayed clear psychomotor delay and behavioural and morphological alterations in the prefrontal cortex, hippocampus and amygdala that were associated with behaviours associated with schizophrenia spectrum disorders in adulthood. We conclude that LCM and its metabolites may have teratogenic effects on the developing embryos, reflected in embryonic lethality and malformations, as well as behavioural and histological alterations in adult mice that resemble those presented by patients with schizophrenia.

ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals.

ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals.

Nėštumų ir gimdymų baigtys po pagalbinio apvaisinimo

Santrauka. Tyrimo tikslas. įvertinti moterų, pastojusių po pagalbinių apvaisinimo budų (PAB), neštumo, gimdymo eigą ir rezultatus bei išanalizuoti naujagimių baigtis. Tyrimo medžiaga ir metodai. 2016–2018 m. laikotarpiu retrospektyviai tirtos 427 pacientės, gimdžiusios Lietuvos sveikatos mokslų universiteto ligoninės Kauno klinikose (toliau – Kauno klinikos), suskirstytos į tiriamąją (n=215) bei kontrolinę (n=212) grupes. Tiriamoji grupė – tai moterys pastojusios po PAB, kontrolinė grupė – tai atsitiktinai atrinktos savaime pastojusios moterys. Analizuoti neštumo, gimdymo eigos ir naujagimių buklės duomenys remiantis gimdymo registro, gimdymo knygų ir ligos istorijomis. Rezultatai. Daugiavaisiai neštumai PAB grupeje sudarė 37,7 proc., o kontrolinėje grupėje – 10,4 proc., p<0,001. Neštumo komplikacijų: preeklampsijos (lengvos, sunkios), neščiųjų hipertenzijos, neščiųjų diabeto dažnis tarp grupių reikšmingai nesiskyrė, p>0,05. Placentos patologijos (įaugusi placenta ir placentos pirmeiga) dažnesnėsPAB grupėje, atitinkamai – p=0,012 ir p=0,004. Priešlaikinio vaisiaus dangalų plyšimo dažnis tarp grupių nesiskyrė. Vaisiaus ydų dažniai abiejose grupėse nesiskyrė, p=0,302. Cezario pjūvio operacijų (CPO) dažnis didesnis PAB grupėje ir siekia 49,8 proc., p=0,016. Placentos atšokos dažnis grupėse nesiskyrė. Apgar balų vidurkis 1 ir 5 min. grupėse nesiskyrė, p1<0,994 ir p5<0,484, tačiau PAB grupėje buvo didesnis neišnešiotų naujagimių, p=0,015, vaisiaus augimo sulėtejimo (VAS), p=0,005 bei mažesnis stambių vaisių dažnis, p=0,005. Išvados. Svarbiausios su PAB susijusios komplikacijos yra daugiavaisiai neštumai, CPO, su placenta susijusios patologijos, priešlaikinis gimdymas, vaisiaus augimo sulėtėjimas.

OP28.10: Routine third trimester ultrasound screening detection rate of congenital anomalies

To evaluate the detection rate of congenital anomalies at the routine third trimester ultrasound screening. We conducted a prospective study of 17063 consecutive pregnancies between 2009 and 2013. In all cases ultrasound screening of congenital defects was carried out at each trimester of the gestation (11-14 weeks; 18-22 weeks; 31-35 weeks). We only included in the study those pregnancies delivered in our hospitals. The overall incidence of fetal malformations was 1.9% (n = 326), of which 31.9% (n = 104) were diagnosed at 11-14 weeks. The following 2nd trimester scan revealed 120 (36.8%) new fetal malformations. An additional 102 (31.3%) structural abnormalities were found in the routine third trimester ultrasound screening. These were mainly abnormalities of the urogenital system (n = 39), followed by congenital heart diseases (n = 28) and central nervous system (n = 12). Third trimester ultrasound presented the best rate for urogenital anomalies, and similar detection rate of the second trimester scan for congenital heart diseases and gastrointestinal system. The 4.1% (n = 5) of congenital anomalies that requested TOP according to our legal framework were diagnosed at third trimester. The ultrasound routine scan in the third trimester increased the detection rate of previously unknown structural abnormalities.

Pregnancy and delivery after liver transplantation

⁎ Corresponding author at: Merkur University Hospital, Zajceva 19, 10000 Zagreb, Croatia. Tel.: +385 994888617. E-mail address: zanazegarac@yahoo.com (Ž. Žegarac). Pregnancy in liver transplant patients is associated with an increased risk of hypertension, pre-eclampsia, preterm delivery, and neonates of low birth weight due to immunosuppressive therapy [1]. Pregnant liver transplant recipients experience a higher incidence of hypertension (34% vs 4%–10%) and preeclampsia (22% vs 6%–8%) compared with the general pregnant population [2,3]. The most common fetal complications in pregnant transplant recipients compared with the general population include prematurity, low birth weight (less than 2500 g), and intrauterine growth restriction [2,4]. The incidence of fetal malformations does not appear to be increased in posttransplant pregnant women compared with the general population, and is approximately 3% [2]. Pregnancies that occur within 12 months of transplantation have a higher incidence of preterm delivery (58% vs 29%), acute rejection of the graft or transplanted liver (50% vs 29%), and cesarean delivery (50% vs 24%) compared with those that occur after 1 year. Cesarean delivery is not indicated for women who have undergone a liver transplant [2]. The present paper reports a successful pregnancy and delivery in a 30-year-old liver transplant recipient who conceived spontaneously 2 years after transplantation. The patient was born in 1976 and received a diagnosis of Wilson disease in 1991. She delivered a male infant in 2001. In 2003, the patient had a therapeutic abortion at 12 weeks of pregnancy owing to portal hypertension. The patient underwent liver transplantation in October 2003 because of advanced liver cirrhosis secondary to a hepatic form of Wilson disease. In 2005, she conceived spontaneously for a third time. Cyclosporine was administered during pregnancy for immunosuppression and whole-blood concentration levels were monitored regularly. The results of all biochemical tests during pregnancy were normal, except platelet count, which ranged from 49–85×10/L. Thrombocytopenia was present before pregnancy, probably as a consequence of spleen enlargement. Fetal ultrasound findings were normal, with fetal growth and development appropriate for gestational age. The patient delivered a male neonate vaginally at 40 weeks of pregnancy. The neonate weighed 4110 g at birth, measured 52 cm in length, and had an Apgar score of 10 at 1, 5, and 10 minutes. Cyclosporine is a potent immunosuppressive medication that may induce vascular endothelial cell dysfunction and reduce nitric oxide production, which may be linked to the development of hypertension [3]. Pregnancy in a patient with previous liver transplantation should be monitored closely. A multidisciplinary approach in pregnancy care is recommended and requires high compliance and motivation of the pregnant patient.

Prenatal developmental toxicity studies on di- n-heptyl and di- n-octyl phthalates in Sprague-Dawley rats

This study evaluates the developmental toxicity of two dialkyl phthalate esters, di- n-heptyl phthalate (DHPP) and di- n-octyl (DnOP) phthalate, which have straight-alkyl side chains of seven and eight carbons, respectively. Sprague-Dawley rats were administered 0, 0.25, 0.50, or 1 g/kg/day of DHPP or DnOP, by gavage, on gestation days 6–20. DHPP and DnOP had no adverse effect on maternal feed consumption and body weight gain, or on the incidence of post-implantation loss and fetal body weight. There was no increase in the incidence of fetal malformations or external and visceral variations, whatever treatment. A significant increase in rudimentary lumbar ribs was observed at all doses of DHPP and DnOP. The anogenital distance of the male fetuses was significantly decreased at the highest dose of DHPP. This parameter was not affected by DnOP. Thus, the lowest-observed-adverse-effect level (LOAEL) for developmental toxicity was 0.25 g/kg/day for DHPP and DnOP.

Fetopathological investigations after induced abortions performed in mid-term gemini pregnancies

Multiple pregnancies present a special obstetric condition whose importance has increased due to the spread of assisted reproductive techniques. We have processed the fetopathological data of 43 abortions induced in mid-term gemini pregnancies, owing to malformations affecting one or both fetuses. 67.4% of the gemini pregnancies were conceived naturally and 32.6% by assisted reproduction techniques. The most commonly occurring malformations affected the fetuses’ cardiovascular and central nervous systems. Positive histories could be detected in 23% of the cases. The male-to-female ratio was found to be 1.14. In the majority of the cases with central nervous system malformation, fetus “A” was affected (85.7%). In 29.4% of the cases, monochorionic placentation was established. Ultrasonography and fetopatological findings yielded perfectly matching results in 78.9% of the cases. The incidence of fetal malformations is probably not higher among fetuses conceived by assisted reproduction techniques compared to the ones conceived naturally. Fetal central nervous system malformations usually affect fetus “A”. Based on the results of the fetopathological examinations, ultrasonography is a reliable method in the diagnostics of malformations affecting twin fetuses. Fetal echocardiography is indicated simply because of the pregnancy being a multiple one.

Is a Routine Ultrasound in the Third Trimester Justified? – Additional Fetal Anomalies Diagnosed After Two Previous Unremarkable Ultrasound Examinations

The detection of fetal structural abnormalities is a routine part of antenatal care. Ultrasound examination policies vary among European countries. An additional ultrasound for fetal structural anomalies in the 3 rd trimester seems important for many reasons. Some abnormalities develop or first become apparent later in pregnancy. The aim of the study was to analyze the rate of previously undetected structural abnormalities in the 3 rd trimester. 8074 fetuses were examined in this prospective study between 1998 and 2008. All received an examination at 11 - 14 weeks and 79 % (6378 / 8074) of these fetuses also received an ultrasound at 20 - 24 weeks. If both of the examinations did not detect structural abnormalities, the fetuses were included in the study group and received an ultrasound at 28 - 32 weeks (n = 5044). New structural abnormalities in the 3 rd trimester were analyzed. The outcome was available in 96 % of the cases. The overall incidence of fetal malformations was 3.6 % (n = 289), of which 40 % (116 / 289) were diagnosed at 11 - 14 weeks. The following 2nd trimester scan revealed 102 (35 %) new fetal malformations. An additional 44 (15 %) structural abnormalities were found in the 3 rd trimester. These were mainly abnormalities of the urogenital system (n = 18). There were also anomalies of the cardiovascular system (n = 9), the gastrointestinal system (n = 6) and the central nervous system (n = 4). One of the cases had a previously undiagnosed abnormal karyotype. The ultrasound examination in the 3 rd trimester is of additional benefit and can detect previously unknown structural abnormalities. These findings are relevant for perinatal management and postnatal follow-up.

Diagnosis and Prognosis of Fetal Malformation by Ultrasonic Tomography

The incidence of fetal malformation was reviewed and an assessment made of the diagnostics of ultrasound. The prognosis of the related cases, as related to the clinical application of ultrasound was discussed. Forty-seven of 56 malformed fetuses were correctly diagnosed antenatally (84%). Diagnostic accuracy in the case of real-time B scan was 91%, while accuracy in the case of contact compound scan was 73%. The disorders most readily identifiable were those related to the image of cystic patterns and/or deformed body contour. Among the 47 with positive findings, an actual plan of treatment was prepared for 9. Of these 9, 6 could actually be treated and the lives of 3 were saved. Deaths were attributed to diagnostic inadequacy, eventual complications and under-development of organs associated with the malformations.

Treatment of Cancer During Pregnancy: The Need for Tailored Strategies

TO THEEDITOR:Van Calsteren et al 1 recently reported a retrospective analysis of 215 patients with cancer who were diagnosed and managed during the course of pregnancy. They showed that managing patients with cancer during pregnancy is feasible and is not associated with an increased risk of fetal malformations. However,theauthorsstatedtheirconcernsregardingthehighincidence of preterm deliveries, which reached 54.2% in their series. They emphasized that preterm delivery is associated with high risk of medicalcomplications,whichcouldhaveseriousconsequenceson fetal morbidity and mortality. In an attempt to reduce this risk, they proposed delaying adjuvant therapy for patients with early breast cancer until fetal maturity, even if this would entail holding therapy up to 3 months. They referred to a mathematical model suggesting that delaying adjuvant therapy in gestational breast cancer could be an acceptable approach. 2 They also suggested that if chemotherapy is considered, delivery should be delayed until fetal maturity rather than fetal viability. We completely agree with the second proposition provided the proper selection of the agents administered during the course of gestation. Nevertheless, although we acknowledge that delaying adjuvant therapy for patients with breast cancer is reasonable in some cases, it remains questionable for many others as a result of the typically aggressive biology of gestational breast cancer. It has been shown that almost 50% of patients with breast cancer diagnosed during pregnancy are diagnosed with locally advanced, node-positivedisease. 3 Furthermore,delayingadjuvantchemotherapy beyond 3 weeks from surgery was shown to be detrimental in patients with endocrine unresponsive tumors. 4 Thus, chemotherapy should not be delayed in pregnant patients with breast cancer whoneedit.Theexceptionwouldbeforpatientsdiagnosedduring the first trimester, in which the incidence of fetal malformation is as high as 20%. 5 Of 83 patients diagnosed with gestational breast cancer, only six infants (7%) had a birth weight below the 10th percentile for gestational age. Other studies showed similar results as well. 6,7 Hence,itisnotclearthatpatientswithearlybreastcancerarethose at significant risk of preterm delivery if exposed to chemotherapy during the pregnancy course. We believe it is hard to generalize conclusions and caution should be taken when dealing with less aggressive settings (eg, adjuvant breast cancer), in which we could compromise their treatment for fear of a risk, which seems to be low anyway in their case. We have recently conducted a systematic review of literature on theuseofdifferentsystemictherapiesinthetreatmentofpatientswith

Effects of Perfluorobutyrate Exposure during Pregnancy in the Mouse

Perfluorobutyrate (PFBA) is a perfluoroalkyl acid (PFAA) found in the environment. Previous studies have indicated developmental toxicity of PFAAs (perfluorooctane sulfonate [PFOS] and perfluorooctanoate [PFOA]); the current study examines that of PFBA. PFBA/NH4(+) was given to timed-pregnant CD-1 mice by oral gavage daily from gestational day (GD) 1 to 17 at 35, 175, or 350 mg/kg (chosen to approximate the developmentally toxic doses of PFOA); controls received water. At GD 18, serum levels of PFBA were 3.8, 4.4, and 2.5 microg/ml, respectively, in the three treated groups. PFBA did not significantly affect maternal weight gain, number of implantations, fetal viability, fetus weight, or incidence of fetal malformations. Incidence of full-litter loss was significantly greater in the 350 mg/kg group, and maternal liver weights were significantly increased in the 175 and 350 mg/kg groups. In contrast to PFOA and PFOS, PFBA exposure during pregnancy did not adversely affect neonatal survival or postnatal growth. Liver enlargement was detected in the PFBA-exposed pups on postnatal day (PD) 1, but not by PD 10. Expression of selected hepatic genes in PFBA-exposed pups at PD 1 did not reveal any significant changes from controls. A significant delay in eye-opening in offspring was detected in all three PFBA groups, and slight delays in the onset of puberty were noted in the 175 and 350 mg/kg groups. These data suggest that exposure to PFBA during pregnancy in the mouse did not produce developmental toxicity comparable to that observed with PFOA, in part, due to rapid elimination of the chemical.

Teratogenesis and immunosuppressive treatment

Despite the potential risks to the mother and fetus caused by immunosuppressive drugs, uneventful pregnancies are now frequent among transplant recipients. Although there is no apparent increase in the type or incidence of malformations in the newborns or evidence of graft dysfunction, pregnancy-related complications, including premature termination and low birth weight, may be more frequent. To prevent graft rejection due to the increased immunologic reactivity of the transplant recipient during pregnancy, it is reasonable to wait 2 years after transplantation before conception, to have stable graft function and to be on low drug doses for maintenance immunosuppression. Among the immunosuppressive agents, corticosteroids may induce a number of treatment-related complications, including diabetes and osteoporosis; however, the incidence of fetal malformations during corticosteroid treatment is about 3.5%, a value close to that of the general population. Among immunosuppressive antibodies, no evidence of developmental toxicity has been demonstrated with basiliximab. On the contrary, some concerns have been raised about azathioprine, since its use has been associated with fetal abnormalities in animals; however, clinical data so far have indicated only a small teratogenic risk. Therefore, immunosuppressive therapy with selected drugs and antibodies does not apparently increase the risk of birth defects and may be continued in pregnancy. Finally, although breast-feeding is not recommended, because of drug transfer into maternal milk, the available clinical data do not support this limitation because of the low amount of drug absorbed by the infant and the absence of clinical toxicity in published case reports.

Incidence of fetal malformations in pregnancies complicated by oligo- and polyhydramnios.

Oligo- and polyhydramnios could be observed in 1%-7% of all pregnancies and are associated with an increased risk of fetal anomalies. We evaluated the fetal outcomes of 840 pregnancies with oligo- and polyhydramnios on the basis of ultrasonographic findings (oligohydramnios: single deepest pocket <2 cm, polyhydramnios: single deepest pocket >8 cm) between 12 and 42 weeks of gestation. We observed 734 pregnancies (752 fetuses) with oligohydramnios and 106 pregnancies (108 fetuses) with polyhydramnios. Of the 752 fetuses with oligohydramnios, 81% survived and 19% died in utero. Among the 108 fetuses of pregnancies with polyhydramnios, 72% of the babies survived and 28% died in utero. In polyhydramnios, 48% (52 of 108) of the fetuses had severe malformations, which is significant compared to the rate of 11.8% (89 of 752) of fetal malformations in oligohydramnios ( P-value<0.001). Oligohydramnios is predominantly associated with malformations of the urinary tract, whereas polyhydramnios is associated with anomalies of the gastrointestinal tract. In conclusion, measurement of single deepest pocket is a valuable screening method to evaluate pregnancies showing the complications of oligo- and polyhydramnios. Pregnancies with severe polyhydramnios have a poorer outcome and fetuses have a significantly higher risk of congenital malformations compared to pregnancies with oligohydramnios.

AN ORAL (GAVAGE) CONTROL EMBRYO-FETAL DEVELOPMENT STUDY IN THE WISTAR HANNOVER RAT

Many of the studies conducted to examine the developmental and reproductive toxicity potential of candidate pharmaceuticals use the Sprague-Dawley rat as the animal model. This is due in part to the large database for this outbred rat available for comparison of litter data, and the low incidence of fetal malformations and variations. The following study was conducted to generate information on potential embryo-fetal developmental defects and litter data in another outbred stock of rat, the Wistar Hannover. One hundred fifty pregnant female Wistar Hannover rats (Tac : Glx : WIfBR) were dosed orally once per day with distilled water from Gestation Days (GD) 6 through 17 covering the time from implantation to closure of the hard palate (GD0 = day of insemination). Caesarean sections were performed on Day 20 of gestation. All fetuses were examined for external, visceral and skeletal malformations and variations. Macroscopic and histomorphologic examinations were also completed for the F0 females at termination. The percent pregnant (88%) and litter size (average 10.6) were found to be lower than that commonly reported for the Sprague-Dawley rat (Crl : CD® (SD)BR; 95.4% and 14.6, respectively). Pre-implantation loss (14.1%), post-implantation loss (7.4%) and percent resorptions (7.2%) occurred at a higher incidence than typically seen in the Sprague-Dawley rat (5.9, 5.6 and 5.1%, respectively). The average fetal body weights for both the female and male rats were lower than those typically seen in the Sprague-Dawley rat. External, visceral and skeletal examination of the F1 fetuses revealed numerous malformations and variations which also occurred at higher incidences than those reported for the Sprague-Dawley rat. Routine macroscopic and histomorphologic examination showed there were no changes that would be interpreted to have impaired mating performance, fertility or gestation. Thus, this study provides information on the reproductive effects and the background incidence of embryo-fetal development defects that could be used for comparison to those identified when using this outbred rat for developmental and reproductive toxicity studies, as well as for comparison to the more commonly used rat stock, the Sprague-Dawley rat. For the parameters evaluated, the Wistar Hannover rat had greater variability and an increased incidence of spontaneous malformations as compared to the Crl : CD® (SD)BR Sprague-Dawley rat. These findings should be considered if this stock of rat is selected in the conduct of developmental and reproductive toxicity studies.

Maternal diabetes and its cell membrane abnormalities as they affect the foetus: implications for the mother and birth defects.

My brief is to discuss maternal diabetes and its implications for birth defects. The perinatal mortality in Britain has fallen in the last 70 years from 60 per 1000 live births to less than 10. For the baby of the diabetic mother there has been a more dramatic decrease from 249 per thousand live births reported by Peel and Oakley in 1949 to approximately 30 in the Swedish cohort in 1993. However even in countries such as Sweden with one of the lowest figures there is still a three fold higher perinatal mortality for the baby of the diabetic mother compared with the background population. There has been a much less dramatic decrease in the incidence of congenital malformations. Peel and Oakley reported an incidence of 6.9% in 1949, and Hanson from Sweden in 1993 reported only a marginally lower incidence of 6.1%. Recent observations indicate that gestational diabetes (GDM) may be associated with increased incidence of fetal malformation and perinatal mortality. The most frequent and significant morbidity is fetal macrosomia, which in turn is associated with increased risk of birth injuries and asphyxia, (Persson and Hanson. 1998). Detection and definition of congenital malformation vary but in spite of this and the much better maternal diabetic control, congenital malformation today forms a major cause of the perinatal morbidity and mortality.

Effects of 5-fluorouracil on cell cycle arrest and toxicity induced by X-irradiation in normal mammalian cells.

From clinical studies in cancer patients and experimental in vitro studies, there is evidence of an increased cytotoxic effect, and even synergy, when irradiation is combined with 5-fluorouracil (5-FU). The mechanism for this is unclear. Mouse fetuses (C3H) have been exposed in vivo to X-irradiation and 5-fluorouracil (5-FU) as single agents or in combination. Cell proliferation, cell cycle progression, fetal survival and incidence of fetal malformations have been studied. The aim of this study was to determine possible synergistic cytotoxic effects when 5-FU and ionizing radiation were combined, particularly concerning the regulation of cell cycle progression in proliferating, non malignant mammalian cells in vivo. The combination of low-toxic doses of X-irradiation and 5-FU had a synergistic toxic effect in nonmalignant mouse fetuses in vivo. The cell cycle regulation was perturbed and the radiation-induced G2-arrest was eradicated by 5-FU during the initial hours. The time for repair of radiation induced DNA-damage is probably reduced, which may explain the increased toxicity of this combination.

WS13‐07The dilemma of selective termination of a malformed fetus in multifetal pregnancy

The incidence of fetal malformation is higher in multifetal pregnancies than in singletons. In a dizygotic twin gestation there is slightly more than twice the risk per pregnancy of a fetal malformation. In a monozygotic twin gestation the rates of chromosomal and mendelian abnormalities are identical to those of a singleton pregnancy. However, there is an increased risk of structural malformations. Selective termination in a bichorionic biamniotic twin pregnancy is done with intracardiac injection of potassium chloride. The international experience show that it can be performed in all 3 trimesters with good outcomes in &gt; 90% of cases and the loss rate is approximately 7%. In monochorionic twin gestation the aim is to arrest the umbilical cord flow completely and permanently. Several methods to achieve this goal are embolization, ligation (fetoscope of U/S guidance), laser coagulation, monopolar and bipolar thermocoagulation. The latter technique became more popular, with estimated loss rate of 20%. The techniques and results will be presented (including video), and the ethical issue will be discussed.

MATERNAL BIOTIN DEFICIENCY CAUSES FETAL MALFORMATIONS BY INDUCING FETAL BIOTIN DEFICIENCY

62 Purpose: In the ICR mouse, maternal biotin deficiency during gestation results in specific fetal malformations (cleft palate, micrognathia, microglossia, and limb hypoplasia). However, the relationships of maternal and fetal biotin status to the incidence of fetal malformations have not been fully elucidated. Description: We sought to determine the effect of various egg-white diets (0, 1, 1.3, 2, 3, 5, 10, and 25%) on (a) the incidence of fetal malformations, (b) maternal biotin status assessed by the urinary excretion rate of 3-hydroxyisovaleric acid (3HIA, an organic acid that arises from the decreased activity of the biotin-dependent enzyme methylcrotonyl-CoA carboxylase), and (c) fetal biotin status as assessed by hepatic biotin and carboxylase activities at gestational day 17. Results: The incidence of fetal malformations increased as maternal and fetal biotin status decreased (Figure). The effect of diet was significant by ANOVA at p < 0.0001 for each malformation. Increasing egg white was associated with increased excretion rates of 3HIA, providing strong evidence that the egg-white diets caused maternal biotin status to decrease. Analysis of maternal and fetal livers from gestational day 17 confirmed an incremental reduction in maternal and fetal biotin status as the percentage of dietary egg-white increased. Conclusion: These data are consistent with the hypothesis that maternal biotin deficiency during gestation induces fetal biotin deficiency, which in turn results in an increased incidence of fetal malformations.FIG