Maternal Insulin-dependent Diabetes Mellitus Research Articles

Holoprosencephaly: The Disease and Its Related Disabilities

AbstractHoloprosencephaly (HPE), the most prevalent developmental anomaly affecting the forebrain in humans, occurs in ∼1 in 16,000 liveborn neonates, with an incidence reaching 1 in 250 in conceptuses. This condition is distributed worldwide. HPE is etiologically heterogeneous, and its pathogenesis is variable. Environmental, teratogenic, genetic, or metabolic factors can contribute to the development of HPE. Notably, maternal insulin-dependent diabetes mellitus and maternal alcoholism are among the primary causative factors. HPE may be linked to various well-defined multiple malformation syndromes characterized by a normal karyotype, such as Smith–Lemli–Opitz's, Pallister–Hall's, or velocardiofacial syndrome. Alternatively, it can be associated with chromosomal abnormalities. (i.e., Patau's syndrome and, less frequently, Edwards' syndrome or Down's syndrome). The major genes implicated in HPE are SHH, ZIC2, SIX3, and TGIF. The range of HPE is extensive, covering diverse neuropathological phenotypes of varying severity. Three classical types of HPE can be distinguished in increasing order of severity: lobar HPE, characterized by separated right and left ventricles with some continuity across the frontal cortex; semilobar HPE, featuring a partial separation; and the most severe form, alobar HPE, where there is a single brain ventricle and the absence of an interhemispheric fissure. Additionally, there are other variations of HPE, ranging in severity, including the less severe interhemispheric median HPE (also known as middle interhemispheric variant). The phenotypic spectrum of HPE is highly extensive, encompassing severe cerebral malformations to microforms. Children with HPE often encounter numerous medical challenges; among them neurological disorders, craniofacial malformations, endocrine disorders, oral and motor dysfunction, and dysfunction of the autonomic nervous system. Neurologic problems, such as cerebral palsy and seizures, are common. The diagnosis of HPE is typically made prenatally, relying primarily on ultrasound and magnetic resonance imaging examinations. The prognosis for individuals with HPE is largely dependent on its underlying causes. Those with cytogenetic abnormalities, in particular, face a significantly poorer prognosis, with only 2% surviving beyond 1 year.

The spectrum of congenital heart defects in neonates of diabetic mothers

Introduction: Insulin-dependent diabetes mellitus (IDDM) in a mother is considered a risk factor for congenital malformation, including congenital heart diseases. Many studies signify a five to six times increased frequency of congenital heart diseases in neonates born from insulin-dependent diabetic mothers. This study aimed to identify the spectrum of congenital heart diseases (CHDs) in neonates born from insulin-dependent diabetes mellitus (IDDM) mothers. Methods: Between April 2019 and March 2021, a descriptive cross-sectional study involved 120 consecutive neonates aged 0-28 days of mothers with insulin-dependent diabetes mellitus (IDDM) at Maiwand Teaching Hospital, Kabul University of Medical Sciences. Neonates born to non-diabetic mothers were excluded. IDDM refers to mothers using Insulin upon admission to control blood glucose. CHD encompasses various heart defects affecting function. Family and maternal history were noted, focusing on health issues and delivery details. Neonatal mothers' ages ranged from 23 to 45 (mean 33), with diabetes onset spanning 2.5 to 25 years. Pediatric cardiologists conducted physical and echocardiographic exams. All CHD forms were documented using 2D echocardiography and Doppler studies (Sono Ace X-6 Machine). Result: 120 consecutive neonates born to mothers with insulin-dependent diabetes mellitus (IDDMs) were investigated during the two-year study period. Of them, 18 (15%) had congenital heart abnormalities. The prevalence of solitary and multiple CHD was 66.6 percent (12 patients) and 33.3 percent (6 patients) in the 18 infants born from IDDMs. The most prevalent isolated defects were PDA (22.2%) and Ventricular septal defect (16.6%). The most common multiple CHDs (16.6 percent) were PDA and ASD. PDA + ASD (16.6%) and VSD + PDA were the most frequent correlations with CHD (11.1 percent). Conclusion: Maternal insulin-dependent diabetes mellitus is an important risk factor for congenital heart disease. Careful assessment and early diagnosis of CHD in this high-risk group are very important in a pediatric population. Expansion of prenatal screening programs for CHDs in mothers suffering from insulin-dependent diabetes mellitus is necessary. Keywords: congenital heart diseases; diabetic mothers; insulin dependent; neonates

Fetal adrenal cortex function in pregnancy, complicated by maternal insulin-dependent diabetes mellitus

Fetal adrenal cortex glucocorticoid andfetal hypophysial adrenocorticotropic function in normal pregnancy and pregnancy, complicated with maternal insulin dependent diabetes mellitus were examined in the present study. Statistically significant feta l hypercortisolemia was observed in pregnancies, complicated by insulin-dependent diabetes mellitus. Correlations between vascular complications o f maternal insulin-dependent diabetes mellitus and fetal cortisol andACTG levels were revealed during the investigation. Severe vascular lesions o f maternal diabetes have been associated with delayed feta l lung maturity. Fetal pulmonary maturity was significantly associated with fe ta l cortisol levels.

Glyoxalase 1 expression is downregulated in preimplantation blastocysts of diabetic rabbits.

In a diabetic pregnancy, an altered maternal metabolism led to increased formation of reactive α-dicarbonyls such as glyoxal (GO) and methylglyoxal (MGO) in the reproductive organs and embryos. The enzyme glyoxalase (GLO) 1 detoxifies reactive α-dicarbonyls thus protecting cells against malfunction or modifications of proteins by advanced glycated end products (AGEs). The aim of this study was to analyse the influence of a maternal insulin-dependent diabetes mellitus (IDD) on GLO1 expression and activity in preimplantation embryos in vivo and human trophoblast cells (Ac-1M88) in vitro. Maternal diabetes was induced in female rabbits by alloxan before conception and maintained during the preimplantation period. GLO1 expression and activity were investigated in 6-day-old blastocysts from healthy and diabetic rabbits. Furthermore, blastocysts and human trophoblast cells were exposed in vitro to hyperglycaemia, GO and MGO and analysed for GLO1 expression and activity. During gastrulation, GLO1 was expressed in all compartments of the rabbit blastocyst. Maternal diabetes decreased embryonic GLO1 protein amount by approx. 30 per cent whereas the enzymatic activity remained unchanged, indicating that the specific GLO1 activity increases along with metabolic changes. In in vitro cultured embryos, neither hyperglycaemia nor MGO and GO had an effect on GLO1 protein amount. In human trophoblast cells, a stimulating effect on the GLO1 expression was shown in the highest GO concentration, only. Our data show that maternal diabetes mellitus affects the specific activity of GLO1, indicating that GLO1 was post-translationally modified due to changes in metabolic processes in the preimplantation embryos.

Trophoblastic microRNAs are downregulated in a diabetic pregnancy through an inhibition of Drosha

MicroRNAs are promising biological markers for prenatal diagnosis. They regulate placental development and are present in maternal plasma. Maternal metabolic diseases are major risk factors for placental deterioration. We analysed the influence of a maternal insulin-dependent diabetes mellitus on microRNA expression in maternal plasma and in blastocysts employing an in vivo rabbit diabetic pregnancy model and an in vitro embryo culture in hyperglycaemic and hypoinsulinaemic medium.Maternal diabetes led to a marked downregulation of Dicer protein in embryoblast cells and Drosha protein in trophoblast cells. MiR-27b, miR-141 and miR-191 were decreased in trophoblast cells and in maternal plasma of diabetic rabbits. In vitro studies indicate, that maternal hyperglycaemia and hypoinsulinaemia partially contribute to the downregulation of trophoblastic microRNAs.As the altered microRNA expression was detectable in maternal plasma, too, the plasma microRNA signature could serve as an early biological marker for the prediction of trophoblast function during a diabetic pregnancy.

Outcomes of Extremely Preterm Infants Born to Insulin-Dependent Diabetic Mothers.

Little is known about in-hospital morbidities and neurodevelopmental outcomes among extremely preterm infants born to women with insulin-dependent diabetes mellitus (IDDM). We examined risks of mortality, in-hospital morbidities, and neurodevelopmental outcomes at 18 to 22 months' corrected age between extremely preterm infants of women with insulin use before pregnancy (IBP), with insulin use started during pregnancy (IDP), and without IDDM. Infants 22 to 28 weeks' gestation born or cared for at a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network center (2006-2011) were studied. Regression models compared the association between maternal IDDM and timing of insulin use and the outcomes of the 3 groups. Of 10 781 infants, 536 (5%) were born to women with IDDM; 58% had IBP, and 36% had IDP. Infants of mothers with IBP had higher risks of necrotizing enterocolitis (adjusted relative risk [RR] = 1.55 [95% confidence interval (CI) 1.17-2.05]) and late-onset sepsis (adjusted RR = 1.26 [95% CI 1.07-1.48]) than infants of mothers without IDDM. There was some indication of higher in-hospital mortality risk among infants of mothers with IBP compared with those with IDP (adjusted RR = 1.33 [95% CI 1.00-1.79]). Among survivors evaluated at 18 to 22 months' corrected age, average head circumference z score was lower for infants of mothers with IBP compared with those without IDDM, but there were no differences in risk of neurodevelopmental impairment. In this cohort of extremely preterm infants, infants of mothers with IBP had higher risks of necrotizing enterocolitis, sepsis, and small head circumference.

Ethmocephaly: A rare cephalic disorder.

Dear Sir, A male neonate, product of nonconsanguineous marriage, was delivered vaginally with severe birth asphyxia (Apgar score 3, 4, 6) to a primiparous woman at 36 weeks’ gestation. The mother did not have any medical illness during pregnancy, and an antenatal ultrasound was performed at 29 weeks’ gestation which revealed holoprosencephaly with midline facial defect in the fetus. Examination after birth revealed weight of 2.6 kg, head circumference 31 cm (<3rd centile), facial dysmorphism (bilateral cleft lip, incomplete cleft palate, a central proboscis with a single nare, hypoplastic eyeballs, low-set ears), short neck with low hairline, widely spaced nipples, sandal gap in both feet, and bilateral simian crease [Figure 1]. He also had a large anterior fontanelle with widely separated sutures. The neonate received resuscitation at birth and was shifted to neonatal intensive care unit. He was put on mechanical ventilation and supportive therapy. Ultrasound of the head revealed undivided cerebral hemispheres with a single ventricle. Our neonate expired at 12 h of life following cardiorespiratory arrest. Karyotyping was performed which was reported as normal. Figure 1 Neonate with bilateral cleft lip, cleft palate, and a central proboscis with single nare and low set ears Ethmocephaly is the rarest phenotypic variant of a group of defects called the holoprosencephaly (HPE) malformation sequence;[1] other variants include cebocephaly, cyclopia, and median cleft palate. HPE is a cephalic disorder characterized by congenital brain malformation due to incomplete cleavage of the prosencephalon occurring between the 18th and 28th day of gestation. HPE is categorized into three levels of increasing severity: Lobar (where the right and left ventricles are separated, but with some continuity across the frontal cortex); semilobar (partial separation of hemispheres), and the most severe form alobar HPE (single brain ventricle and no interhemispheric fissure).[2] HPE can be caused by both genetic and environmental factors such as maternal insulin-dependent diabetes mellitus (1% risk of HPE),[3] maternal alcoholism, prenatal exposure to teratogens (alcohol, retinoic acid, cholesterol biosynthesis inhibitors, and maternal infections (cytomegalovirus, toxoplasmosis, rubella).[4] Some genetic associations with trisomy 13 or 18 have been reported.[5] Multiple malformation syndromes such as Kallmann syndrome, Pallister–Hall, Smith–Lemli–Opitz, and CHARGE syndrome have been found to be associated with HPE. However, nearly 70% cases are sporadic. Nearly all HPE malformation disorders have a fatal outcome during gestation or in early infancy. HPE can be detected by ultrasonography in the first trimester. Ultrasonographic markers include hypertelorism and a single common cerebral ventricle with absent midline echo. Other investigations include chromosomal analysis by karyotyping and genetic mutation analysis by denaturing high-performance liquid chromatography and multiplex polymerase chain reaction. Ethmocephaly is a rare cephalic disorder with a reported incidence of 1 in 15,000 among live births and 1 in 250 among abortuses.[1] It characterized by HPE with an undivided cerebrum and a single ventricle. In addition, there is a midline facial anomaly associated with a central proboscis, two well-formed orbits with absent or hypoplastic eyeballs, hypotelorism, and low set ears. It is differentiated from other HPE disorders namely cyclopia where the two eyes are fused together in a single median orbit and from cebocephaly which is characterized by a flattened nose with single nostril located below close-set eyes, based on the phenotype. Our case presented with midline facial defects, hypotelorism, bilateral microphthalmos, a central proboscis and bilateral low set ears, and alobar HPE, which are characteristic of ethmocephaly. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Prenatal diagnosed caudal regression syndrome

Background: Caudal regression syndrome (CRS) is a rare complex congenital anomaly which is characterized by agenesis of the sacral and lumbar spine. Pelvis, lower extremity, genitourinary, cardiac anomalies and lower extremity neurological and motor development deficits may be accompanied. The exact etiology is unclear but the maternal insulindependent diabetes mellitus (hyperglycaemia during embryogenesis seems to act as a teratogen), genetic factors, vascular hypoperfusion may play a role in the etiology. Case: A 41-year-old gravida 4, para 2, live 1, abortus 1 patient with 35 weeks of gestation. The patient had 12-year history of type 1 diabetes mellitus. In ultrasonographic examination we found the length of the bones (all the upper and lower bones) 8 weeks underdeveloped and didn’t observe the lumbar, sacral vertebrae and iliac bones. Lower extremities were crossed in froglike position, there wasn’t lower extremity movements. Due to sacral agenesia the head of the femurs were closer. Also pes equinovarum deformity, single umbilical artery, kidneys in contact at the midline were present. All of these findings indicated the diagnosis of caudal regression syndrome. Conclusion: Diabetes is increased fetal anomalities in pregnancy. Diabetic pregnancy should be more evaluated than pregnancies with no risk. Antenatal care should be done more carefully. Especially, prenatal maternal blood glucose levels and HbA1cis most important for prevention of fetal anomalities.

Bilateral Renal Agenesis/Hypoplasia/Dysplasia (BRAHD): Postmortem Analysis of 45 Cases with Breakpoint Mapping of Two De Novo Translocations

BackgroundBilateral renal agenesis/hypoplasia/dysplasia (BRAHD) is a relatively common, lethal malformation in humans. Established clinical risk factors include maternal insulin dependent diabetes mellitus and male sex of the fetus. In the majority of cases, no specific etiology can be established, although teratogenic, syndromal and single gene causes can be assigned to some cases.Methodology/Principal Findings45 unrelated fetuses, stillbirths or infants with lethal BRAHD were ascertained through a single regional paediatric pathology service (male∶female 34∶11 or 3.1∶1). The previously reported phenotypic overlaps with VACTERL, caudal dysgenesis, hemifacial microsomia and Müllerian defects were confirmed. A new finding is that 16/45 (35.6%; m∶f 13∶3 or 4.3∶1) BRAHD cases had one or more extrarenal malformations indicative of a disoder of laterality determination including; incomplete lobulation of right lung (seven cases), malrotation of the gut (seven cases) and persistence of the left superior vena cava (five cases). One such case with multiple laterality defects and sirelomelia was found to have a de novo apparently balanced reciprocal translocation 46,XY,t(2;6)(p22.3;q12). Translocation breakpoint mapping was performed by interphase fluorescent in-situ hybridization (FISH) using nuclei extracted from archival tissue sections in both this case and an isolated bilateral renal agenesis case associated with a de novo 46,XY,t(1;2)(q41;p25.3). Both t(2;6) breakpoints mapped to gene-free regions with no strong evidence of cis-regulatory potential. Ten genes localized within 500 kb of the t(1;2) breakpoints. Wholemount in-situ expression analyses of the mouse orthologs of these genes in embryonic mouse kidneys showed strong expression of Esrrg, encoding a nuclear steroid hormone receptor. Immunohistochemical analysis showed that Esrrg was restricted to proximal ductal tissue within the embryonic kidney.Conclusions/SignificanceThe previously unreported association of BRAHD with laterality defects suggests that renal agenesis may share a common etiology with heterotaxy in some cases. Translocation breakpoint mapping identified ESRRG as a plausible candidate gene for BRAHD.

A re‐evaluation of the influence of maternal insulin‐dependent diabetes on fetal nuchal translucency thickness and first‐trimester maternal serum biochemical markers of aneuploidy

To evaluate the influence of maternal insulin-dependent diabetes mellitus (IDDM) on maternal serum free ß-hCG, pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency (NT) thickness from 11 weeks to 13 weeks 6 days of gestation in a large cohort of women screened prospectively for chromosomal anomalies. Information on maternal IDDM status, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records. On total, the control group included 83,972 and the IDDM group included 489 pregnancies. The median-corrected free β-hCG and PAPP-A, expressed as MoM, and fetal NT, expressed as delta values, in the IDDM and non-IDDM groups were compared. There were no significant differences between the IDDM and non-IDDM groups in median-corrected free β-hCG (IDDM 1.01 MoM, non-IDDM 1.01 MoM; p = 0.970), or mean delta NT (IDDM 0.00 mm, non-IDDM 0.02 mm; p = 0.412). However, the median-corrected PAPP-A was significantly lower (IDDM 0.88 MoM, non-IDDM 1.03 MoM; p < 0.0001). In pregnancies with maternal IDDM, first-trimester screening for chromosomal defects does not require adjustments for the measured fetal NT and maternal serum free ß-hCG. However, for PAPP-A the 15% reduction is large enough to require correction in the calculation of risks for chromosomal defects.

Outcome of ante-natally suspected congenital cardiac conditions in Wales over a period of 7 years 2002–2008

AimTo determine the reasons, outcome of ante-natally detected congenital heart conditions, incidence with associated co-morbid conditions and the recurrence rate of congenital heart conditions with maternal and fetal conditions in...

Hypoglycemia Rates in the First Days of Life among Term Infants Born to Diabetic Mothers

Objectives: To discover the risk factors for developing hypoglycemia in newborns born to diabetic mothers and to characterize the rates of glucose concentrations in the first two days of life. Methods: Retrospective recordings of medical charts of 576 healthy term infants of diabetic mothers during an 18-month period. We determined the following pre-feeding glucose concentrations: ‘normoglycemia’ (≥47 mg/dl = 2.6 mmol/l), ‘mild hypoglycemia’ (40–46 mg/dl = 2.2– 2.5 mmol/l), ‘moderate hypoglycemia’ (30–39 mg/dl = 1.7–2.1 mmol/l) and ‘severe hypoglycemia’ (<30 mg/dl = 1.7 mmol/l). Results: Glucose concentrations below ‘normoglycemia’ and ‘severe hypoglycemia’ were observed in 280 (48.6%) and 23 (4%) of the infants, respectively. The main risk factors for developing glucose concentrations below ‘normoglycemia’ in the first day of life were large size for gestational age and maternal insulin-dependent diabetes mellitus. ‘Severe hypoglycemia’ was more common among infants born to mothers who needed insulin (either type A2 or insulin-dependent diabetes mellitus). Infants born to mothers with insulin-dependent diabetes mellitus were less mature, heavier, large for their gestational age and exhibited more ‘severe and moderate hypoglycemia’ in the first day of life as compared to infants born to diabetes type A1 and A2 mothers. In addition, infants who were large for gestational age tended to have more ‘moderate hypoglycemia’ when born to diabetes type A1 mothers compared to small and appropriate-for-gestational-age infants. Thirty infants (5%) still had hypoglycemia on the second day of life. This subgroup of infants did not differ with regard to maternal-type diabetes. Conclusions: Infants born to diabetic mothers tend to have a high rate of hypoglycemia on the first day of life when a relatively high cut-off point (≥47 mg/dl = 2.6 mmol/l) is used. Infants born large for gestational age as well as those born to mothers with juvenile diabetes mellitus are at higher risk and should be closely monitored.

VACTERL association and maternal diabetes: A possible causal relationship?

Some factors(s)/features(s) of maternal insulin-dependent diabetes mellitus are considered common human teratogens. Although the variable association of cardiac, renal, and skeletal anomalies are commonly observed in infants from diabetic mothers, the relationship between VACTERL (i.e., the association of vertebral and cardiac defects, tracheo-esophageal fistula, renal/radial malformations, and other limb anomalies) and maternal diabetes has not been sufficiently emphasized in the literature. We report on a 3-year-old boy presenting with a constellation of blastogenetic malformations strongly suggestive of VACTERL association. His mother was affected by insulin-dependent diabetes since she was 7 years old and pregnancy history disclosed very high glucose and HbA1c levels, especially during the first 2 gestational months. In an attempt to properly counsel the parents, we reviewed the literature and identified four additional patients with VACTERL and first trimester exposure to maternal diabetes mellitus. Although this evidence does not strongly support a causal relationship between these two conditions, additional arguments may substantiate this hypothesis. The pathogenesis of diabetic embryopathy in relation to the VACTERL phenotype is also discussed.

Perinatal Factors Associated With Cerebral Palsy in Children Born in Sweden

To identify perinatal factors associated with cerebral palsy (CP). This was a case-control study based on the Swedish Medical Birth Registry and the Swedish Hospital Discharge Registry, including 2,303 infants born in Sweden 1984-1998 with a diagnosis of CP and 1.6 million infants without this diagnosis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Infants born preterm had a highly increased risk for CP, and constituted 35% of all cases; OR 34 (95% CI 29-39) in weeks 23-27, OR 37 (95% CI 32-42) in weeks 28-29, OR 26 (95% CI 23-30) in weeks 30-31, and OR 3.9 (95% CI 3.4-4.4) in weeks 32-36. Boys had a higher risk (sex ratio 1.36:1), particularly before term (sex ratio 1.55:1). Other factors associated with CP were being small or large for gestational age at birth, abruptio placentae (OR 8.6, 95% CI 5.6-13.3), maternal insulin-dependent diabetes mellitus type 1 (OR 2.1, 95% CI 1.4-3.1), preeclampsia (OR 1.5, 95% CI 1.3-2.4), being a twin (OR 1.4, 95% CI 1.1-1.6), maternal age older than 40 years (OR 1.4, 95% CI 1.1-1.8) or 35-39 years (OR 1.2, 95% CI 1.1-1.4), primiparity (OR 1.2, 95% CI 1.1-1.3), and smoking (OR 1.2, 95% CI 1.1-1.3). In term infants, low Apgar scores were associated with a high risk for CP; OR 62 (95% CI 52-74) at score 6 at 5 minutes, OR 498 (95% CI 458-542) at score 3. Other factors associated with CP in term infants were breech presentation at vaginal birth (OR 3.0, 95% CI 2.4-3.7), instrumental delivery (OR 1.9, 95% CI 1.6-2.3), and emergency cesarean delivery (OR 1.8, 95% CI 1.6-2.0). Preterm birth entails a high risk for CP, but 65% of these children are born at term. Several obstetric factors and low Apgar scores are associated with CP. II-2.

The influence of maternal insulin‐dependent diabetes on fetal nuchal translucency thickness and first‐trimester maternal serum biochemical markers of aneuploidy

To evaluate the influence of maternal insulin dependent diabetes mellitus (IDDM) on maternal serum free beta-hCG, PAPP-A and fetal nuchal translucency (NT), thickness at 11 to 13(+6) weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies. Information on maternal IDDM status, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two first-trimester screening centres. In total the control group included 33 301 pregnancies of which 16 366 had NT and maternal serum biochemistry results and 16 305 with NT only. The IDDM group included 195 pregnancies of which 79 had NT and maternal serum biochemistry results and 127 with NT only. The median maternal weight corrected free beta-hCG and PAPP-A, expressed as multiple of the median (MoM), and fetal NT, expressed as delta values, in the IDDM and non-IDDM groups were compared. There were no significant differences between the IDDM and non-IDDM groups in median maternal weight corrected free beta-hCG (IDDM 0.87 MoM, 95% Confidence Interval 0.75 to 1.16 MoM, non-IDDM 1.00 MoM), median maternal weight corrected PAPP-A (IDDM 1.02 MoM, 95% Confidence Interval 0.83 to 1.05 MoM, non-IDDM 1.01 MoM), or mean delta NT (IDDM 0.0358 mm, non-IDDM 0.0002 mm). In pregnancies with maternal IDDM, first-trimester screening for chromosomal defects does not require adjustments for the measured fetal NT. However, more data are required before the possible reduction in maternal serum free beta-hCG and the reduction of PAPP-A suggested by the published world series can be considered sufficiently important to take into account in the calculation of risks for chromosomal defects.

Technical standards and guidelines: Prenatal screening for open neural tube defects: This new section on “Prenatal Screening for Open Neural Tube Defects,” together with the new section on “Prenatal Screening for Down Syndrome,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories

Technical standards and guidelines: Prenatal screening for open neural tube defects: This new section on “Prenatal Screening for Open Neural Tube Defects,” together with the new section on “Prenatal Screening for Down Syndrome,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories *

Technical standards and guidelines: Prenatal screening for Down syndrome: This new section on “Prenatal Screening for Down Syndrome,” together with the new section on “Prenatal Screening for Open Neural Tube Defects,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories

Technical standards and guidelines: Prenatal screening for Down syndrome: This new section on “Prenatal Screening for Down Syndrome,” together with the new section on “Prenatal Screening for Open Neural Tube Defects,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories *

Congenital heart disease in infants of diabetic mothers: echocardiographic study.

Our objective was to study neonates born to insulin-dependent diabetes mellitus (IDDM) mothers to detect the spectrum of congenital heart disease (CHD). Between July 2000 and June 2001, a prospective study of 100 consecutive infants of diabetic mothers (IDMs) at King Khalid University Hospital in Riyadh was undertaken. Family and maternal history, physical examination with special attention to the cardiovascular system, and echocardiography were performed. A total of 100 consecutive IDMs examined. The most common echocardiographic findings were patent ductus arteriosus (PDA; 70%), patent foramen ovale (68%), atrial septal defect (5%), small muscular ventricular septal defect (4%), mitral valve prolapse (2%), and pulmonary stenosis (1%). Hypertrophic cardiomyopathy (HCMP) was observed in 38% of cases, mainly hypertrophy of the interventricular septum. Severe forms of CHD encountered were D-transposition of great arteries, tetralogy of Fallot, and hypoplastic left heart syndrome (1% each). Isolated aortic stenosis and coarctation of aorta were not encountered in this series. Overall incidence of congenital heart disease was 15% after excluding PDA and HCMP. Maternal IDDM is a significant risk factor for CHD. Careful evaluation and early diagnosis of CHD in this high-risk group are highly indicated. There is a need for development of prenatal screening programs for CHD in our population.

Management issues for women with epilepsy: neural tube defects and folic acid supplementation.

For infants exposed to antiepileptic drugs (AEDs) in utero, the risk for congenital malformations is approximately 4 to 6%, twice the rate reported in the general population. A variety of malformations have been reported in association with prenatal exposure to AEDs. However, a particular association of valproate and carbamazepine with neural tube defects (NTDs)--specifically, with spina bifida aperta (SB)--has been identified. The prevalence of SB is approximately 1 to 2% with valproate exposure and 0.5% with carbamazepine. Reported risk factors for NTDs include previous pregnancy with an NTD, maternal insulin-dependent diabetes mellitus, various nutritional deficiencies and occupational exposures, and high prepregnancy weight. Deficiencies of folate have been implicated in the development of birth defects, including NTDs. The value of periconceptional folic acid supplementation for women in the general population is accepted. However, it is unclear whether folic acid supplementation protects against the embryotoxic and teratogenic effects of AEDs because animal and human studies and case reports have shown variable results. Nevertheless, folic acid supplementation is recommended for women with epilepsy as it is for other women of childbearing age. Even with supplementary folic acid, women taking valproate or carbamazepine should undergo perinatal diagnostic ultrasound to rule out NTDs.

Impaired vascular reactivity in pregnant women with insulin-dependent diabetes mellitus

Objective: The purpose of this study was to investigate the vascular function of pregnant women with insulin-dependent diabetes mellitus, using a noninvasive method. Study Design: This was a cross-sectional study that examined vascular function, which was assessed by flow-mediated dilatation of the brachial artery, in 37 pregnant women with insulin-dependent diabetes mellitus and in 37 healthy pregnant women at 20 weeks of gestation. The control of diabetes was also assessed by the measurement of glycosylated hemoglobin. Data were analyzed by 2-sided unpaired t test and multivariate regression analysis.Results: In the pregnant women with insulin-dependent diabetes mellitus, flow-mediated dilatation of the brachial artery was significantly lower than in healthy pregnant women (6.43% ± 3.66% vs 9.43% ± 3.69%, respectively; P =.0008). This difference was apparent even after an adjustment was made for blood vessel diameter, which was different between the 2 populations (P =.01). Flow-mediated dilatation in diabetic women was significantly correlated with the duration of diabetes (P =.01) but not with the levels of glycosylated hemoglobin. Conclusion: Maternal insulin-dependent diabetes mellitus is associated with an impaired vasodilatory response to a blood flow stimulus. This vascular dysfunction is associated with the duration of the diabetes.(Am J Obstet Gynecol 2002;186:84-8.)