Evidence Of Congenital Malformations Research Articles

Leucism: the prevalent congenital malformation in the olive ridley sea turtle of northwestern Mexico

Despite being the most abundant sea turtle in the world, the olive ridley turtle Lepidochelys olivacea is classified as Vulnerable by the IUCN. There is evidence of congenital malformations in hatchlings, and the associated causes are multifactorial, with both genetic and environmental sources. Santuario Playa Ceuta (SPC) is a sanctuary for the olive ridley, located at the northernmost region of its nesting range in the Mexican Pacific. The objective of this study was to identify and quantify the prevalence and severity of congenital malformations in olive ridley embryos/hatchlings in SPC during the 2017 nesting season. We collected 62907 eggs from 643 relocated nests that were moved to a hatchery, of which 4242 eggs with obvious development did not hatch and were analyzed for this study. Hatching success was 53.9%, with 22.5% of nests (n = 145) and 0.54% of eggs (n = 344) showing embryos or hatchlings with malformations. The nest severity index was 2.4 (range: 1-10) malformed embryos or hatchlings per nest, and the organism severity index was 1.4 (range: 1-7) malformations per malformed embryo or hatchling. Leucism was the most prevalent malformation (34.4%; 170/494 total observed), with the craniofacial region showing the greatest diversity of malformations (17/35 types). Given the geographical position of SPC, extreme environmental conditions (e.g. cold, heat, and dryness) could be one of the main causes of teratogenesis in this species. However, more studies are needed regarding the presence of contaminants, genetic factors, health assessments of nesting females, and malformation rates of nests that remain in situ versus those that are relocated.

Use of erlotinib throughout pregnancy: a case-report of a patient with metastatic lung adenocarcinoma.

The use of erlotinib throughout pregnancy has not been previously reported. We present the case of a 40 yearold female patient with stage IV lung adenocarcinoma, mediastinal, bone and cerebral metastasis, a EGFR mutation and no smoking history, who had begun first line treatment with erlotinib 150 mg once daily. After two and a half months of treatment a fourteen-week pregnancy was documented, and after informing on fetal risks secondary to erlotinib use and maternal risks secondary to treatment withholding, she decided to continue with treatment under clinical surveillance by both the oncology and obstetrics clinics. At thirty-three weeks gestation a live born 1600 g female was born by caesarean section without evidence of congenital malformations. Imaging assessment after eight months of treatment showed complete bone and central nervous system response and partial lung and mediastinal response. The patient is currently undergoing the 11th month of treatment and is asymptomatic, the baby is 4 months old and is in good health.

Use of erlotinib throughout pregnancy: A case-report of a patient with metastatic lung adenocarcinoma

The use of erlotinib throughout pregnancy has not been previously reported. We present the case of a 40year-old female patient with stage IV lung adenocarcinoma, mediastinal, bone and cerebral metastasis, a EGFR mutation and no smoking history, who had begun first line treatment with erlotinib 150mg once daily. After two and a half months of treatment a fourteen-week pregnancy was documented, and after informing on fetal risks secondary to erlotinib use and maternal risks secondary to treatment withholding, she decided to continue with treatment under clinical surveillance by both the oncology and obstetrics clinics. At thirty-three weeks gestation a live born 1600g female was born by caesarean section without evidence of congenital malformations. Imaging assessment after eight months of treatment showed complete bone and central nervous system response and partial lung and mediastinal response. The patient is currently undergoing the 11th month of treatment and is asymptomatic, the baby is 4months old and is in good health.

Analysis of Anteroposterior Renal Pelvic Diameter in Normal Human Fetuses: Anatomical Reference for Antenatal Ultrasound Examination in Fetal Renal Pelvis Dilatation

Purpose Fetal renal pelvis dilatation (FRPD) is the most frequently detected abnormality on prenatal ultrasound. The anteroposterior diameter of renal pelvis (APDRP) is the most reproducible measurement of FRPD. The APDRP diameter cutoffs are not well standardized, which may result in conflicting prenatal ultrasound. The objective of this work is to assess the measures of the APDRP in human fetuses. Material and Methods We analyzed 64 human fetuses (35 males and 29 females) totalizing 128 renal units. The fetuses were macroscopically well preserved and no external evidence of congenital malformations was detected. The fetuses were evaluated with regard to the foot length, crown-rump length and body weight. The fetuses were dissected with the aid of a stereoscopic lens with 16/25X magnification. The renal pelvis was dissected and the APDRP was made using a precision digital paquimeter. Renal length, width and thickness also were obtained. To compare the quantitative data in both sexes the Students t-test was used (p Results Gestational age ranged from 12 to 25 weeks post conception (WPC). The mean APDRP in male fetuses was 3.64mm (2.02 to 5.45mm) to the right side and 3.58mm (1.7 to 4.94mm) to the left side (no statistics difference: p Conclusions Our results suggest that the limit of 4mm for APDRP in fetuses could be considered normal in the second trimester.

Management of malignant gliomas during pregnancy

Limited data are available on the management of glioma in pregnant women. Therefore, the aim of the current article was to describe the outcome of women with malignant gliomas who were exposed to chemotherapy early in the gestation period of their pregnancies. The authors presented a case series of 6 women with malignant gliomas who during glioma-directed treatment were discovered to have an unplanned pregnancy. All patients elected to discontinue chemotherapy and carry their pregnancy to term. All women had uneventful pregnancies with no glioma-related complications. All women delivered healthy newborns without evidence of congenital malformations despite exposure to cytotoxic chemotherapy and anticonvulsant medications. Management of malignant glioma during pregnancy is challenging; however, normal delivery and healthy live birth is possible.

Risperidone Therapy in Two Successive Pregnancies

Risperidone Therapy in Two Successive Pregnancies

Risperidone Therapy in Two Successive Pregnancies

There is very limited information available on the use of psychotropic drugs in consecutive pregnancies. The authors report a case of a woman with schizophrenia wherein risperidone was used successfully in two consecutive pregnancies. This is only the second known report in the existing literature in which atypical antipsychotic was used successfully in two successive pregnancies.

Erlotinib administration for advanced non-small cell lung cancer during the first 2 months of unrecognized pregnancy

Although several antineoplastic agents have been proven to be safe for the fetus after the organogenesis period, there is limited information on their use during the first trimester of pregnancy. Herein we report the first case of a patient with metastatic lung cancer treated with erlotinib during the first 2 months of an unrecognized pregnancy. A 30-year-old woman was diagnosed with stage IV non-small cell lung cancer with bone and lung metastasis. The patient received 4 months of palliative cisplatin/gemcitabine chemotherapy and biphosphonates. After 12 months the disease progressed and the patient received erlotinib 100 mg/day. During this period the patient became pregnant. Since she recalled the date of her last menstrual period at about 15 days prior to the start of the therapy, we did consider the possibility of conception at the time of the first day of erlotinib administration. Informed about the risk for the fetus due to erlotinib, the patient stopped anticancer treatment. After 42 weeks of regular gestation, cesarean section was performed, delivering a 3490 g female new-born with no evidence of congenital malformations. The disease evaluation performed with thoracic CT scan, after 1 month from the childbirth, showed a progressive lung metastasis and erlotinib treatment was resumed at the dose of 150 mg/day.

Docetaxel, gemcitabine, and cisplatin administered for non-small cell lung cancer during the first and second trimester of an unrecognized pregnancy

Although several chemotherapeutic agents have been proven to be safe for the fetus after the organogenesis period, there is limited information on their use during the first trimester of pregnancy. We here report the first case of a patient with lung cancer who was treated with platinum-based chemotherapy from the first trimester of an unrecognized pregnancy. A 35-year-old woman was diagnosed with stage IV non-small cell lung cancer with brain metastasis. Since she recalled the date of her last menstrual period at about 20 days prior to consult, we did not consider the possibility of conception at the time of diagnosis. With an object of controlling the increased intracranial pressure, we initially performed a craniotomy with tumor removal, followed by whole brain irradiation. Without our knowledge of her pregnancy, she received a palliative chemotherapy with docetaxel and cisplatin followed by gemcitabine and cisplatin as the second-line chemotherapeutic agents between weeks 9 and 22 of gestation. Follow-up computed tomographic scans performed 2 months after the last chemotherapy showed a fetus in the patient's abdomen. Cesarean section was performed at 33 weeks of gestation, delivering a 1490 g female newborn with no evidence of congenital malformations.

The first case of mitoxantrone exposure in early pregnancy

Mitoxantrone is an antineoplastic agent considered a potential human teratogen because of its mechanism of action and is classified by the US Food and Drug Administration in pregnancy category risk D. In the literature there are only four cases of women exposed to the drug in late pregnancy. We report the first case of mitoxantrone therapy in the first trimester and during the pregnancy. A 41-year-old woman affected with multiple sclerosis, conceived during therapy and continued mitoxantrone until 29 weeks and 3 days of her pregnancy. She delivered by cesarean section at 39 weeks a growth restricted female baby weighing 1950 g without evidence of congenital malformations.

Wilms Tumor in Monozygous Twins

The concomitant occurrence of Wilms tumor (WT) was observed in two monozygotic twin sisters without evidence of congenital malformations. Twin 1 was diagnosed with a stage I WT at 11 months of age, whereas twin 2 developed a bilateral (stage V) WT at 13 months of age. In both cases pathologic examination showed a nonanaplastic stromal type WT, with marked rhabdomyomatous elements. Cytogenetic analyses performed on blood samples and on tumor specimens revealed no karyotypic abnormality. No alteration of the WT1 and POU6F2 genes was identified in constitutional and tumor DNA of both sisters, and no anomaly in WT1 expression was evidenced in the normal kidney of one of them. However, loss of heterozygosity on chromosome 11p, involving the alleles of maternal origin, was detected both in the single tumor of twin 1 and in the two distinct tumors of twin 2, thus suggesting a common etiology of the diseases. To the authors' knowledge, this is the first report describing at both the clinical and genetic level a couple of monozygotic twins concordant for WT development.

Safety of Clozapine in 2 Successive Pregnancies

Dear Editor: With the introduction of atypical antipsychotics, it was predicted that the incidence of hyperprolactinemia-induced infertility problems would decrease. However, the use of atypical antipsychotics during pregnancy is an area with more questions than answers. We present a case wherein clozapine therapy was continued successfully over 2 consecutive pregnancies. case Report MK, aged 25 years and a housewife of rural background, was premorbidly well adjusted, with a family history of depression. She had an acute-onset 7-year continuous illness precipitated by the death of her father. The illness was characterized by auditory hallucinations (that is, commenting and commanding), tac tile hallucinations, passivity phenomenon, aggression, negative symptoms, and disturbed biofunctions. There was no history suggestive of depression or mania, substance abuse, or head injury. During this period, treatment tolerance or resistance was seen with various antipsychotics (that is, chlorpromazine, haloperidol, trifluperazine, and risperidone). Hence, clozapine was initiated after baseline investigations up to 400 mg daily. With 8 months of treatment, significant improvement in psychopathology and functioning occurred, with associated weight gain of 10 kg. Over the next 3 years, clozapine was gradually reduced to 200 mg daily with no reemergence of positive symptoms but persistence of negative symptoms. MK was married in early 2001 and continued to take clozapine. She was informed about the risk of congenital malformations with antipsychotics and was advised to use contraception. However, she conceived after 6 months of marriage and continued with the pregnancy and with clozapine. Venereal Disease Research Laboratory Slide Test (VDRL), HIV, and hepatitis B surface antigen titers were negative during the first trimester, and there was no evidence of congenital malformations during antenatal ultrasonography on repeat occasions. Hemoglobin was 9.6 gram percent at the 10th week of pregnancy; folic acid and iron supplements were initiated at 10 and 16 weeks, respectively. Pregnancy-induced hypertension (PIH) was detected at the 38th week and was monitored. At the beginning of the 39th week, a 3-kg boy was delivered by episiotomy, with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. The postnatal period was uneventful, with normal developmental growth until age 20 months. Eight months after the first delivery, the patient reconceived and continued the pregnancy while on clozapine 100 mg daily. PIH occurred at 30 weeks and was managed with methyldopate hydrochloride 1500 mg daily. At 39 weeks, a 2.8-kg girl in breech presentation was delivered by elective cesarean section. …

Third-trimester maternal glucose levels from diurnal profiles in nondiabetic pregnancies: correlation with sonographic parameters of fetal growth.

To assess the 24-h glucose levels in a group of nondiabetic, nonobese pregnant women and to verify the presence of correlations between maternal glucose levels and sonographic parameters of fetal growth. A total of 66 Caucasian nonobese pregnant women with normal glucose challenge tests (GCT) enrolled in the study; from this population, we selected 51 women who delivered term (from 37 to 42 weeks completed) live-born infants without evidence of congenital malformations. The women were requested to have three main meals and to perform daily glucose profiles fortnightly from 28-38 weeks without modifying their lifestyle or following any dietary restriction. All subjects were taught how to monitor their blood glucose by using a reflectance meter. Fetal biometry was evaluated by ultrasound scan according to standard methodology at 22, 28, 32, and 36 weeks of pregnancy. The overall daily mean glucose level during the third trimester was 74.7 +/- 5.2 mg/dl. Daily mean glucose values increased between 28 (71.9 +/- 5.7 mg/dl) and 38 (78.3 +/- 5.4 mg/dl) weeks of pregnancy. We found a significant positive correlation at 28 weeks between 1-h postprandial glucose values and fetal abdominal circumference (AC). At 32 weeks, we documented positive correlations between fetal AC and maternal blood glucose levels 1 h after breakfast, 1 and 2 h after lunch, and 1 and 2 h after dinner. At 36 weeks, there was a positive correlation between fetal AC and 1- and 2-h postprandial blood glucose levels. In addition, there was a negative correlation between head-abdominal circumference ratio and 1-h postprandial blood glucose values. This longitudinal study first provides a contribution toward the definition of normoglycemia in nondiabetic, nonobese pregnant women; moreover, it reveals significant correlations of postprandial blood glucose levels with the growth of insulin-sensitive fetal tissues and, in particular, between 1-h postprandial blood glucose values and fetal AC.

Genetic and reproductive toxicity of butadiene and isoprene

Butadiene (BD) and its 2-methyl analogue, isoprene, have been extensively studied in animals and BD in population studies. Both chemicals are metabolised by liver cytochrome P450 dependent monogenases to monoepoxide and diepoxide intermediates. The diepoxide intermediates of both compounds were mutagenic in Salmonella typhimurium. However, unlike the monoepoxide of BD, the monoepoxides of isoprene were not mutagenic. It appears that they have no alkylating capacity. BD did not induce somatic cell mutation and recombination or sex-linked recessive lethal mutation in Drosophila melanogaster and isoprene produced no increase in chromosomal aberrations in CHO cells in vitro. Comparative concentrations of haemoglobin adducts in the blood of mice and rats after exposure to BD indicated that reaction with blood may decrease the levels of reactive intermediates available to tissues in rats, but not in mice contributing to greater potency of BD in the mouse. For isoprene, the adducts reach approximately the same concentrations in both species. DNA adducts have also been detected in testicular and lung cells of mice after BD exposure. The level of epoxybutene haemoglobin adducts was significantly elevated in BD-exposed workers, but lower than in rats and mice. In conjunction with the toxicology and carcinogenesis studies for BD and isoprene, additional mice were included for the evaluation of cytogenetic effects. Both chemicals produced increases in sister chromatid exchanges in bone marrow cells and in the frequency of micronuclei in normochromatic and polychromatic erythrocytes, but only BD produced an increase in the percent of bone marrow cells with chromosomal aberrations. At similar doses, the effects with BD were 2–3 times larger than with isoprene. There were also increased hprt mutation frequencies in rats and mice after BD exposure. Biomonitoring studies with hprt mutations in lymphocytes showed conflicting results, with both positive and negative findings. BD has been shown to be positive in one human cytogenetic biomonitoring study and not in three others, but chromosomal aberrations were increased in BD-exposed workers after challenge with gamma rays. Re-analysis of GSTTI null individuals showed positive results. There was an increase in spermatid micronuclei in mice by BD and its metabolites and in rats only by its metabolites. The cytotoxic response of germ cells in mice is greater than in rats. Dominant lethal mutations have been induced by BD and diepoxybutane, but not by epoxybutene. There was some evidence of congenital malformations in mice after BD exposure and there was a linear concentration-related induction of heritable translocations in mice. There was no induction of dominant lethal mutations or congenital malformations in rats. Using the heritable translocation data in mice, it has been determined that if a worker is continually exposed over 5 or 6 weeks to 20–25 ppm of BD, the risk of producing a child with a balanced reciprocal translocation is twice as high as the background risk. Since genetic damage cannot be measured directly in human germ cells, risk to such cells can also be estimated from germ cells and somatic cells of the mouse and human somatic cells using the parallelogram approach. Using doubling doses, the fourth corner of the parallelogram was calculated as a doubling dose for human germ cells of 4390 ppm/h. However, it is still questioned if man is more like rat than mouse in terms of sensitivity to exposure. Similar germ cell data do not exist for isoprene. In conventional developmental studies, where rats and mice were exposed to BD, maternal toxicity was shown in rats but there was no evidence of developmental toxicity or teratogenic effects and there was a small effect on sperm morphology. After exposure to isoprene, there was no adverse effect on rat dams or other reproductive indices. In mice, there was reduced foetal body weight and decreased maternal weight gain and isoprene also affected ovarian follicles. There was a reduction in testicular function parameters such as testicular weight and sperm motility.

Successful use of pentoxifylline in male-factor infertility and previous failure of in vitro fertilization: A prospective randomized study

Our objective was to determine whether the use of pentoxifylline (PF) would improve the in vitro fertilization (IVF) rate and outcome in couples with male factor infertility and previous failure of fertilization in vitro. This prospective randomized controlled study was conducted in an assisted conception unit. Forty-nine couples with previous failed fertilization in vitro attributable to male factor or male-factor infertility without previous IVF were recruited for the study. Controlled ovarian hyperstimulation was performed using a combination of gonadotropin releasing hormone agonist and human menopausal gonadotropin. Oocytes of the same grade and maturity were inseminated with spermatozoa treated with PF or control spermatozoa. A maximum of three embryos was replaced after 48 hr and all other embryos were cryopreserved. Pregnancy outcome was followed up and evidence of fetal or neonatal anomalies reported. A significantly higher fertilization rate occurred in the group where oocytes were inseminated with spermatozoa treated with PF compared with controls (56.3 versus 30.7%; P < 0.05). Fertilization occurred in 45 of the 49 cycles (92%). In seven cycles, only the oocytes that were inseminated with spermatozoa treated with PF fertilized, in contrast to only one cycle where the oocytes inseminated with control sperm fertilized (P < 0.05). Fifty-seven PF and 31 control embryos were replaced and 11 clinical pregnancies occurred. Three of the pregnancies occurred in the seven cycles in which only PF embryos were replaced, one in the single cycle where control embryos were replaced and seven from the 37 cycles in which both PF and control embryos were replaced. There was no evidence of congenital malformations in any of the offsprings resulting from this study. This study suggests that PF improves the fertilization rate and outcome in couples with male factor infertility and poor fertilization rates. This study does not suggest any increase in teratogenicity or evidence of congenital malformations in pregnancies following IVF cycles where PF was used.

Case report 832

A 6-day-old boy presented at the Orthopaedic Depar tment of the University of Mfinster in February 1987 with a swelling of the right lower limb (just below the proximal tibial epiphysis). The swelling had existed since birth. Physical examination revealed a swelling and minimal tenderness in the region of the right proximal end of the right tibia. Motion of the right knee was normal. Otherwise, the patient was healthy with no evidence of congenital malformations. The laboratory data were normal. Radiological studies showed a lytic lesion in the left proximal tibial metadiaphysis (Figs. 1, 2) with extension into adjacent soft tissue structures. A biopsy was performed.

Non-Hodgkin's lymphomas and pregnancy: Presentation of 16 cases

Chemotherapy and obstetric care of 16 pregnant patients with non-Hodgkin's lymphoma are reported in this paper. All patients received chemotherapy during the various trimesters of pregnancy, including 8 cases during the first trimester, and there was no evidence of congenital malformations in any offspring. Fifteen babies are alive, healthy, and at a normal level of growth 3 to 11 years after birth. Eight mothers who achieved complete remission are alive and free of disease, 4 to 9 years after delivery, without maintenance treatment and would be considered cured. On the basis of the present study it was concluded that pregnancy is not a contraindication for treatment of non-Hodgkin's lymphomas, cytotoxic drugs do not necessarily cause congenital malformations, and long-term remission can be achieved in these mothers.

Children born after their fathers had been treated with chemotherapy for testicular cancer

Twenty children fathered by 15 patients treated with platinum-based combination chemotherapy for disseminated testicular carcinoma were examined and found to have no evidence of congenital malformations. The results indicate no reason for advising against pregnancies in this group of young couples.

Drug Influences on Malformations

Confirmed evidence of congenital malformations caused by drug exposure is difficult to obtain because of limitations in methods of study. The case against exogenous female hormones, the benzodiazepines, amphetamines, and clomiphene citrate has not been proved, but oral anticoagulants, anticonvulsants, tri-methadione, and lithium have recently been added to the list of human teratogens.