Decreased neonatal morbidity in 'stomach-down' left congenital diaphragmatic hernia: implications of prenatal ultrasound diagnosis for counseling and postnatal management.

OBJECTIVE: To evaluate the influence of stomach position on postnatal outcome in cases of left congenital diaphragmatic hernia (CDH) without liver herniation, diagnosed and characterized on prenatal ultrasound (US), by comparing those with ('stomach-up' CDH) to those without ('stomach-down' CDH) intrathoracic stomach herniation. METHODS: Infants with left CDH who underwent prenatal US and postnatal repair at our institution between January 2008 and March 2017 were eligible for inclusion in this retrospective study. Detailed prenatal US examinations, fetal magnetic resonance imaging (MRI) studies, operative reports and medical records of infants enrolled in the pulmonary hypoplasia program at our institution were reviewed. Cases with liver herniation and those with an additional anomaly were excluded. Cases in which bowel loops were identified within the fetal chest on US while the stomach was intra-abdominal were categorized as having stomach-down CDH. Cases in which bowel loops and the stomach were visualized within the fetal chest on US were categorized as having stomach-up CDH. Prenatal imaging findings and postnatal outcomes were compared between the two groups. RESULTS: In total, 152 patients with left CDH were initially eligible for inclusion. Seventy-eight patients had surgically confirmed liver herniation and were excluded. Of the 74 included CDH cases without liver herniation, 28 (37.8%) had stomach-down CDH and 46 (62.2%) had stomach-up CDH. Of the 28 stomach-down CDH cases, 10 (35.7%) were referred for a suspected lung lesion. Sixty-eight (91.9%) cases had postnatal outcome data available for analysis. There was no significant difference in median observed-to-expected (o/e) lung-area-to-head-circumference ratio (LHR) between cases with stomach-down CDH and those with stomach-up CDH (41.5% vs 38.4%; P = 0.41). Furthermore, there was no difference in median MRI o/e total lung volume (TLV) between the two groups (49.5% vs 44.0%; P = 0.22). Compared with stomach-up CDH patients, stomach-down CDH patients demonstrated lower median duration of intubation (18 days vs 9.5 days; P < 0.01), median duration of extracorporeal membrane oxygenation (495 h vs 223.5 h; P < 0.05), rate of supplemental oxygen requirement at 30 days of age (20/42 (47.6%) vs 3/26 (11.5%); P < 0.01) and rate of pulmonary hypertension at initial postnatal echocardiography (28/42 (66.7%) vs 9/26 (34.6%); P = 0.01). No neonatal death occurred in stomach-down CDH patients and one neonatal death was seen in a patient with intrathoracic stomach herniation. CONCLUSIONS: In infants with left CDH without liver herniation, despite similar o/e-LHR and o/e-TLV, those with stomach-down CDH have decreased neonatal morbidity compared to those with stomach herniation. Progressive or variable physiological distension of the stomach over the course of gestation may explain these findings. Stomach-down left CDH is mistaken for a lung mass in a substantial proportion of cases. Accurate prenatal US characterization of CDH is crucial for appropriate prenatal counseling and patient management. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Noninvasive assessment of fetal central nervous system insult: Potential application to prenatal diagnosis.

OBJECTIVE: We have developed novel methods for isolating fetal central nervous system (CNS)-derived extracellular vesicles (FCEs) from maternal plasma as a non-invasive platform for testing aspects of fetal neurodevelopment in early pregnancy. We investigate the hypothesis that levels of defined sets of functional proteins in FCEs can be used to detect abnormalities in fetal neuronal and glial proliferation, differentiation, and survival. METHOD: Maternal plasma was obtained between 10 and 19 weeks from women with current heavy EtOH exposure and matched controls. FCE levels of synaptophysin, synaptotagmin, synaptopodin, and neurogranin were quantified normalized to the exosome marker CD81. Quantitative RT-PCR was performed with specific primers for miR-9. RESULTS: FCE cargo protein levels of synaptophysin, synaptotagmin, synaptopodin, and neurogranin were all significantly reduced in pregnancies exposed to current heavy EtOH use (P < .001 for all). Both synaptophysin and neurogranin appeared to be particularly discriminatory with no overlap between exposed and control subjects. Up to tenfold inhibition (90%) in MicroRNA-9 was observed in FCEs from EtOH exposed fetuses compared with controls. CONCLUSION: Our results suggest that FCEs purified from maternal plasma may be a powerful tool to assess abnormal proliferation and differentiation of CNS stem cells as early as the late first trimester. What's already known about this topic? Exosomes/extracellular vesicles (ECVs) are emerging as exciting novel biomarkers in neurologic disease (Alzheimers) What does this study add? Evidence that Fetal CNS ECVs can be isolated from maternal blood The origin of the ECVs appears to be the fetal brain and not the placenta Findings with ECVs correlates with fetal exposure to alcohol. Potential for first trimester prenatal diagnosis of fetal neurologic disease.

The ratio of cavum septi pellucidi width to anteroposterior cerebellar diameter: A novel index as a diagnostic adjunct for prenatal diagnosis of trisomy 18.

AIM: To explore the effectiveness of cavum septi pellucidi (CSP) width to anteroposterior cerebellar diameter (APCD) ratio as a diagnostic adjunct for prenatal diagnosis of trisomy 18. METHODS: Images of normal fetal brain within 15 and 35 weeks were stored in our center from 2016 to 2017. Images of aneuploid fetuses were retrospectively collected from 2004 to 2017. The transverse cerebellar diameter, APCD and CSP width were measured. CSP/APCD and APCD/transverse cerebellar diameter ratios were calculated and compared between euploid and aneuploid fetuses. RESULTS: One thousand and forty one fetuses were analyzed, including 817 euploid fetuses and 224 aneuploid fetuses (trisomy 21 117 cases, trisomy 18 82 cases, trisomy 13 9 cases, sex-linked 16 cases). No correlation had been found between both ratios and gestational weeks (P > 0.05). In aneuploid groups, means of ratios were both significantly different just between trisomy 18 group and euploid group (P < 0.05). The best area under the curve was shown by the CSP/APCD ratio. The cutoff value of CSP/APCD was 0.46 (sensitivity 87.0%, specificity 85.0%). CONCLUSION: A wide CSP or cerebellar hypoplasia warrants a more detailed ultrasound screening and genetic counseling. A larger CSP/APCD ratio alerts us to trisomy 18 syndrome, especially in cases with subtle anomalies.

No. 365-Fetal and Perinatal Autopsy in Prenatally Diagnosed Fetal Abnormalities with Normal Chromosome Analysis.

OBJECTIVE: To review the information on fetal and perinatal autopsies, the process of obtaining consent, and the alternative information-gathering options following a prenatal diagnosis of non-chromosomal anomalies in order to assist health care providers in providing postnatal counselling regarding diagnosis and potential recurrence risks. OUTCOMES: To provide better counselling about fetal and perinatal autopsies for women and families who are dealing with a prenatally diagnosed non-chromosomal fetal anomaly. EVIDENCE: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2010, 2011, and 2017, using appropriate key words (fetal autopsy postmortem, autopsy, perinatal postmortem examination, autopsy protocol, postmortem magnetic resonance imaging, autopsy consent, tissue retention, autopsy evaluation). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. BENEFITS, HARMS, AND COSTS: This update educates readers about (1) the benefits of a fetal perinatal autopsy, (2) the consent process, and (3) the alternatives when the family declines autopsy. It also highlights the need for a standardized approach to fetal and perinatal autopsies, emphasizing pertinent additional sampling when indicated. The authors recognize that there is variability across Canada in access to the cited services and resources. As such, these recommendations were developed in an attempt to promote access and to provide a minimum standard for all provinces and territories across the country. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table).

Genotoxic Effects in Human Fibroblasts Exposed to Microwave Radiation.

In the last decades, technological development has led to an increasing use of devices and systems based on microwave radiation. The increased employment of these devices has elicited questions about the potential long-term health consequences associated with microwave radiation exposure. From this perspective, biological effects of microwave radiation have been the focus of many studies, but the reported scientific data are unclear and contradictory. The aim of this study is to evaluate the potential genotoxic and cellular effects associated with in vitro exposure of human fetal and adult fibroblasts to microwave radiation at the frequency of 25 GHz. For this purpose, several genetic and biological end points were evaluated. Results obtained from comet assay, phosphorylation of H2AX histone, and antikinetochore antibody (CREST)-negative micronuclei frequency excluded direct DNA damage to human fetal and adult fibroblasts exposed to microwaves. No induction of apoptosis or changes in prosurvival signalling proteins were detected. Moreover, CREST analysis showed for both the cell lines an increase in the total number of micronuclei and centromere positive micronuclei in exposed samples, indicating aneuploidy induction due to chromosome loss.

Embryo-fetal toxicity assessment of vonoprazan in rats and rabbits.

Vonoprazan is a new potassium-competitive acid blocker to treat acid-related diseases. However, its safety during pregnancy is unclear. The aim of the study was to investigate the potential reproductive toxicity on the embryo-fetal development of vonoprazan. Vonoprazan acetate was administered by intravenous injection to pregnant rats (0, 2, 6 and 20 mg kg-1 day-1 ) and rabbits (0, 1.2, 3.6 and 12 mg kg-1 day-1 ) during the organogenetic period (gestation day 6-15 [rats] and 6-18 [rabbits]). Maternal reproductive endpoints were evaluated, together with effects on fetal growth and morphological development. In rats, no treatment-related effects were found in the highest dose group (20 mg kg-1 ) and the maternal plasma exposure was ≥50-fold the expected clinical human exposure. However, in rabbits, dose-related clinical signs (soft or liquid feces) occurred in the 12 mg kg-1 group, which was regarded as a maternal toxicity. Besides, decreased maternal weight gain also was considered as a minimal maternal toxicity. At 12 mg kg-1 , delayed fetal ossification was found as evidence of embryo-fetal growth retardation, which was related to decreased fetal and placental weights. There was no maternal and developmental toxicity in the 1.2 and 3.6 mg kg-1 groups. Thus, the no-observed-adverse-effect levels of vonoprazan acetate in rabbits are considered 3.6 mg kg-1 day-1 , which produced plasma exposure that was about 18-fold human clinical exposure.

Third trimester growth restriction patterns: individualized assessment using a fetal growth pathology score.

OBJECTIVE: To qualitatively and quantitatively characterize third trimester growth patterns in fetuses/neonates with growth restriction using Individualized Growth Assessment. METHODS: Serial fetal size measurements from 73 fetuses with proven growth restriction were evaluated using a novel composite parameter, the Fetal Growth Pathology Score (FGPS1). Third trimester FGPS1 measurements plotted against fetal age were examined for patterns. Identified patterns were characterized using the four components of the FGP1 [head circumference (HC), abdominal circumference (AC), femur diaphysis length (FDL), estimated weight (EWT)]. A secondary characterization using age of onset, duration and magnitude of the growth abnormality process was also performed. Frequencies and magnitudes of abnormal values in different FGPS1 patterns were compared. RESULTS: Five growth restriction patterns were found in 70/73 (95.9%) of the cases, with progressive worsening [Pattern 1 (37.0%)] and abnormal growth identified only at last scan [Pattern 2 (27.4%)] being the most common. These two patterns were usually statistically different from each other and the other three with respect to size parameter abnormalities and abnormal growth process characteristics (MANOVA). Growth abnormalities in all parameters of the FGPS1 contributed to the five abnormality patterns although AC and EWT were most important. The age of onset, duration and magnitude were similar between patterns except for Pattern 2, which had a late onset and a short duration (GLM + contrasts). CONCLUSIONS: Our study represents the first detailed evaluation of third trimester growth restriction using methods that consider the growth potential of each fetus. Five distinctive and repetitive patterns were found, suggesting that fetal growth restriction evolves in different ways. Further research is needed to determine the relationships of these patterns to physiological/biochemical changes and adverse outcomes associated with growth restriction.

Virtual histological assessment of the prenatal life history and age at death of the Upper Paleolithic fetus from Ostuni (Italy).

The fetal remains from the Ostuni 1 burial (Italy, ca 27 ka) represent a unique opportunity to explore the prenatal biological parameters, and to reconstruct the possible patho-biography, of a fetus (and its mother) in an Upper Paleolithic context. Phase-contrast synchrotron X-ray microtomography imaging of two deciduous tooth crowns and microfocus CT measurements of the right hemimandible of the Ostuni 1b fetus were performed at the SYRMEP beamline and at the TomoLab station of the Elettra - Sincrotrone laboratory (Trieste, Italy) in order to refine age at death and to report the enamel developmental history and dental tissue volumes for this fetal individual. The virtual histology allowed to estimate the age at death of the fetus at 31-33 gestational weeks. Three severe physiological stress episodes were also identified in the prenatal enamel. These stress episodes occurred during the last two months and half of pregnancy and may relate to the death of both individuals. Compared with modern prenatal standards, Os1b's skeletal development was advanced. This cautions against the use of modern skeletal and dental references for archaeological finds and emphasizes the need for more studies on prenatal archaeological skeletal samples.

Assessment of Structural and Functional Abnormalities of the Myocardium and the Ascending Aorta in Fetus with Hypoplastic Left Heart Syndrome.

Aims. To detect anatomical and intrinsic histopathological features of the ascending aorta and left ventricular (LV) myocardium and evaluate right ventricular (RV) function in fetuses with hypoplastic left heart syndrome (HLHS). Methods. Twenty-five fetuses diagnosed with HLHS were followed up in the antenatal and postpartum periods. 12 necropsy heart specimens were analyzed for morphological and histological changes. Results. Prenatal echocardiography and pathologic anatomy displayed the typical characteristics of HLHS as a severe underdevelopment of the LV in the form of mitral stenosis or atresia or as aortic atresia or stenosis, with a decreased ratio of aortic diameter to pulmonary artery diameter (median of 0.49 with a range of 0.24 to 0.69, p ≤ 0.001) and a higher ratio of RV diameter to LV diameter (median of 2.44 with a range of 1.33 to 6.25, p ≤ 0.001). The RV volume, stroke volume, and cardiac output in HLHS fetuses were increased compared with the gestational age-matched normal controls (p < 0.01). Histological changes in the 12 HLHS specimens included LV myocardial fibrosis, aortic elastic fragmentation, and fibrosis. Conclusions. In addition to severe anatomical deformity, distinct histological abnormalities in the LV myocardium and aortic wall were identified in the fetuses with HLHS. RV function damage may be potentially exists.

The use of imaging technology in the assessment of the fetal inflammatory response syndrome-imaging of the fetal thymus.

The fetal inflammatory response syndrome (FIRS) describes a state of extensive fetal multi organ involvement during chorioamnionitis, and is associated with grave implications on perinatal outcome. The syndrome has been linked to the preterm parturition syndrome and is associated with inflammation/infection processes in most of the fetal organs. The fetal thymus, a major organ in the developing immune system involutes during severe neonatal disease and has been shown to be smaller in fetuses with FIRS. Various methods for imaging of the fetal thymus and measurement are described. Currently the only method to diagnose FIRS prenatally is through amniocentesis. We suggest that women who are admitted with preterm labor with intact membranes and those with PPROM should have a detailed sonographic examination of the fetal thymus as a surrogate marker of fetal involvement in intrauterine infection/inflammation processes.

[Postmortem assessment of labor from changes in the skull and brain in fetuses and newborn infants].

The paper gives data on the ways of identifying the pattern of head insertion, wire point, the degree of head flexion and extension, asynclitism, and configuration from the fetal and neonatal skull. The findings are important for the assessment of the course of labor and the quality of its management and for the diagnosis of birth injury. Emphasis is laid on the significance of brain compression in the genesis of fetal asphyxia.

Assessment of "fresh" versus "macerated" as accurate markers of time since intrauterine fetal demise in low-income countries.

OBJECTIVE: To compare provider assessment of fetal maceration with death-to-delivery interval to evaluate the reliability of appearance as a proxy for time of death. METHODS: Cohort chart abstraction was performed for all stillbirth deliveries at or above 28 weeks of gestation during a 1-year period in a teaching hospital in Ghana. RESULTS: Of 470 stillborn infants, 337 had adequate data for analysis. Of 47 fetuses alive on admission with death-to-delivery intervals estimated to be less than 8 hours (expected to be reported as fresh), 14 (30%) were actually reported as macerated. Of 94 cases in which the fetus was deceased on admission with death-to-delivery interval of more than 8 hours (expected to be macerated), 17 (18%) were described as fresh. CONCLUSION: Provider description of fetal appearance may be an unreliable indicator for time since fetal death. The findings have significant implications for stillbirth prevention and assessment.

The novel use of a heterozygous knockout mouse for embryofetal development assessment of a glucokinase activator.

Glucokinase activators (GKAs), such as AZD1656, are designed as antihyperglycemic agents for diabetics and can cause dose-limiting hypoglycemia in normal animals used in embryofetal development studies. Genetically modified heterozygous GK knockout (gkdel/wt) mice are less susceptible to severe GKA-induced hypoglycemia than wild-type mice due to their elevated baseline glucose levels. In this study, the gkdel/wt mouse was used as an alternative rodent strain for embryofetal development studies with AZD1656. Heterozygous global knockout gkdel/wt females were dosed with 20, 50, or 130 mg/kg/day of AZD1656 or vehicle for a minimum of 14 consecutive days before mating with wild-type males and throughout organogenesis. Maternal effects were confined to slightly reduced food consumption, reduced body weight gain, and the pharmacologic effect of decreased plasma glucose. Fetuses were genotyped. Fetal weights at the high dose were slightly reduced but there was no effect on fetal survival. There were two specificmajormalformations, omphalocele and right-sided aortic arch, with increased fetal incidence in mid- and high-dose fetuses (e.g., omphalocele fetal incidence of 0.6, 0.7, 4.6, and 2% across the dose groups) plus increased incidences of minor abnormalities and variants indicative of either delayed or disturbed development. Fetal weight and abnormalities were unaffected by fetal genotype. The fetal effects are considered hypoglycemia related. There was no effect on embryofetal survival in the gkdel/wt mouse at AZD1656 exposures, which were 70× higher than those causing 75% fetal death in rabbits. This illustrates the value of genetically modified animals in unraveling target versus chemistry-related effects.

Assessment of genotoxicity of aluminium acetate in bone marrow, male germ cells and fetal liver cells of Swiss albino mice.

Aluminium acetate (AA) has many pharmaceutical applications, which necessitates a thorough evaluation of its toxicity. Dose- and time-dependent genotoxic effects of AA were investigated in Swiss albino mice after exposure via intraperitoneal (i.p.) injection, by employing assays to detect chromosomal aberrations (CA) and micronuclei (MN) in bone marrow, MN in fetal liver, and abnormalities in sperm. Animals were treated with single doses of 50, 100 and 150mg/kg body weight (bw), and with daily doses of 50mg/kg bw for seven consecutive days, in order to study the effects of acute and cumulative doses, respectively. Post-treatment sampling was done at 24, 48 and 72h for bone-marrow CA and MN tests, to study time-dependent effects. Both single and repeated exposures of AA induced chromosomal aberrations, which were dose and time-dependent. The MN test failed to demonstrate genotoxicity after the single-dose exposures, indicating that a higher threshold dose is required for MN induction. Repeated treatment of AA, however, induced MN formation even at the low dose (P<0.05), reflecting genotoxicity following chronic/sub-chronic exposure. A significant reduction in mitotic index and in the P/N (polychromatic/normochromatic erythrocytes) ratio suggests that AA also has a mitodepressive effect in bone-marrow cells. AA-induced germinal genotoxicity was evident from a significant and dose-dependent increase in the percentage of abnormal spermatozoa and a reduction in sperm count. Transplacental exposure of AA resulted in the dose-dependent increase in the frequency of micronucleated erythrocytes in the developing fetus. Thus, the current in vivo study revealed genotoxic effects of AA both on somatic and germ cells of Swiss albino mice.

Accounting for the professional work of pathologists performing autopsies.

CONTEXT: With an increasing trend toward fee-code-based methods of measuring the clinical professional productivity of pathologists, those pathologists whose clinical activities include the performance of autopsies have been disadvantaged by the lack of generally accepted workload equivalents for autopsy performance and supervision. OBJECTIVE: To develop recommended benchmarks to account for this important and often overlooked professional activity. DESIGN: Based on the professional experience of members of the Autopsy Committee of the College of American Pathologists, a survey of autopsy pathologists, and the limited additional material available in the literature, we developed recommended workload equivalents for the professional work associated with performing an autopsy, which we elected to express as multiples of established Current Procedural Terminology codes. RESULTS: As represented in Table 3 , we recommend that the professional work associated with a full adult autopsy be equivalent to 5.5 × 88309-26. Additional professional credit of 1.5 × 88309-26 should be added for evaluation of the brain and for a detailed clinical-pathologic discussion. The corresponding value for a fetal/neonatal autopsy is 4.0 × 88309-26. CONCLUSION: Although we recognize that autopsy practices vary significantly from institution to institution, it is hoped that our proposed guidelines will be a valuable starting point that individual practices can then adapt, taking into account the specifics of their practice environment.

Pain assessment in human fetus and infants.

In humans, painful stimuli can arrive to the brain at 20-22 weeks of gestation. Therefore several researchers have devoted their efforts to study fetal analgesia during prenatal surgery, and during painful procedures in premature babies. Aim of this paper is to gather from scientific literature the available data on the signals that the human fetus and newborns produce, and that can be interpreted as signals of pain. Several signs can be interpreted as signals of pain. We will describe them in the text. In infants, these signs can be combined to create specific and sensible pain assessment tools, called pain scales, used to rate the level of pain.

Noninvasive assessment of antenatal hydronephrosis in mice reveals a critical role for Robo2 in maintaining anti-reflux mechanism.

Antenatal hydronephrosis and vesicoureteral reflux (VUR) are common renal tract birth defects. We recently showed that disruption of the Robo2 gene is associated with VUR in humans and antenatal hydronephrosis in knockout mice. However, the natural history, causal relationship and developmental origins of these clinical conditions remain largely unclear. Although the hydronephrosis phenotype in Robo2 knockout mice has been attributed to the coexistence of ureteral reflux and obstruction in the same mice, this hypothesis has not been tested experimentally. Here we used noninvasive high-resolution micro-ultrasonography and pathological analysis to follow the progression of antenatal hydronephrosis in individual Robo2-deficient mice from embryo to adulthood. We found that hydronephrosis progressed continuously after birth with no spontaneous resolution. With the use of a microbubble ultrasound contrast agent and ultrasound-guided percutaneous aspiration, we demonstrated that antenatal hydronephrosis in Robo2-deficient mice is caused by high-grade VUR resulting from a dilated and incompetent ureterovesical junction rather than ureteral obstruction. We further documented Robo2 expression around the developing ureterovesical junction and identified early dilatation of ureteral orifice structures as a potential fetal origin of antenatal hydronephrosis and VUR. Our results thus demonstrate that Robo2 is crucial for the formation of a normal ureteral orifice and for the maintenance of an effective anti-reflux mechanism. This study also establishes a reproducible genetic mouse model of progressive antenatal hydronephrosis and primary high-grade VUR.

Quality assessment of perinatal and infant postmortem examinations in Turkey.

An autopsy examination is important in identifying the cause of death and as a means of auditing clinical and forensic practice; however, especially in perinatal and infantile age groups determining the cause of death leads to some difficulties in autopsy practice. In this study, 15,640 autopsies recorded during the years 2000-2004 in the Mortuary Department of the Council of Forensic Medicine were reviewed. Autopsy findings of 510 cases between 20 completed weeks of gestation and 1 year of age were analyzed retrospectively. The quality of each necropsy report was assessed using a modification of the system gestational age assessment described by Rushton, which objectively scores aspects identified by the Royal College of Pathologists as being part of a necropsy. According to their ages, the cases were subdivided into three groups. Intrauterine deaths were 31% (158 cases), neonatal deaths were 24% (123 cases), and infantile deaths were 45% (229 cases) of all cases. Scores for the quality of the necropsy report were above the minimum acceptable score with 44% in intrauterine, 88% in neonatal and infantile deaths.

Assessment of teratogenecity and embryotoxicity of sludge from textile industries at Pali (India) in Swiss albino mice exposed during organogenetic period.

The present investigation was carried out to assess the teratological effects of in-utero exposure of sludge leachate from textile and dyeing industries located in Pali, Rajasthan. Sludge was collected at the combined effluent treatment plant (CETP). Two groups of 10 pregnant Swiss albino mice each, were given sludge leachate of 1/10 and 1/100 dilutions with water ad libitum from 6th day to 15th day of gestation covering the critical period of organogenesis. Cesarean sections were performed on day 18 of gestation and all foetuses were examined for reproductive and teratological tests. Sludge induced maternal toxicity was evidenced by significant increase in leachate consumption, reduction in body weight gain and reduction in fur of the body. Developmental toxicity was evidenced by a significant decrease in foetal weight per litter increase in the number of resorptions and an increase in total number of foetuses showing bone retardation and skeletal variations (specially of skull, sternebrae and vertebrae). The leachate of the sludge that is being dumped in the open areas of the town Pall seems to elicit teratogenic as well as embryotoxic potential as indicated by the findings of the present investigation.