The Significance of Exposure to Pregestational Type 2 Diabetes in Utero on Fetal Renal Size and Subcutaneous Fat Thickness.

Objectives: To determine the relationship between exposure to pregestational type 2 diabetes (T2D) and renal size and subcutaneous fat thickness in fetuses during routine obstetrical ultrasound. Methods: This was a case-control study (January 1, 2019 to December 31, 2019). Routine obstetrical ultrasounds performed between 18 and 22 weeks' gestation at a tertiary-care fetal assessment unit were reviewed. "Cases" comprised ultrasounds of fetuses exposed to pregestational T2D in utero. The control group was assembled from ultrasounds of healthy controls. Postprocessing measurements of fetal renal size and abdominal wall thickness from stored images were performed by two independent observers, and findings were compared between groups. Results: There were 54 cases and 428 ultrasounds of healthy controls. The mean maternal age of cases was 32.1 years (SD 6.2) compared to 33.2 years (SD 5.3) for healthy controls, and the majority of ultrasounds were performed in multiparous patients (83%). At the 18 to 22 week ultrasound, there was a significant reduction in renal size amongst fetuses exposed to maternal T2D in utero compared to controls; among cases, the mean renal width was 8.0 mm (95% CI 7.8-8.1) compared to 11.4 mm (95% CI 10.6-12.7) in controls (p < 0.0001); the mean renal thickness among cases was 8.1 mm (95% CI 7.9-8.2) compared to 11.5 mm (95% CI 10.7-12.9) in controls (p=0.001). There was no obvious difference in estimated fetal weight between groups, yet fetuses exposed to maternal T2D had increased subcutaneous abdominal wall fat thickness at this early gestational age (p=0.008). Conclusions: Fetal renal size in cases exposed to pregestational T2D is significantly smaller compared to controls, and subcutaneous abdominal wall fat is significantly thicker. Given emerging evidence about the developmental origins of disease, further study is needed to correlate the association between fetal renal size and fat distribution in the fetus and the long-term risk of chronic renal disease and diabetes in these offspring.

Severe Rh alloimmunization and hemolytic disease of the fetus managed with plasmapheresis, intravenous immunoglobulin and intrauterine transfusion: A case report.

Rh alloimmunization remains a potentially devastating complication of pregnancy, with fetal anemia causing hydrops and intrauterine death. Intrauterine transfusion is the standard treatment, but is particularly dangerous before 20 weeks gestation. When the need for intrauterine transfusion is anticipated early in pregnancy, immune-modulating therapies such as plasmapheresis and IVIG have been used to delay transfusion to a later gestational age. We report a 35-year-old G5P1 Rh(D)-negative woman with severe Rh alloimmunization managed successfully with sequential plasmapheresis, intravenous immune globulin and intrauterine transfusion. The optimal plasmapheresis treatment protocol and incremental benefit of IVIG remains unknown.

Increased nuchal translucency thickness: a potential indicator for Ritscher-Schinzel syndrome.

OBJECTIVE: The Ritscher-Schinzel syndrome (RSS), also known as the 3C syndrome, is an autosomal recessive disorder classically comprising craniofacial, cerebellar and cardiac defects. The underlying molecular etiology remains unknown; therefore, prenatal diagnosis of recurrences depends on identification of the associated structural anomalies on second trimester ultrasound examination. Identification of recurrences using first-trimester ultrasound has not been reported previously. METHODS: Two women who presented at our center with fetal nuchal abnormalities on first trimester ultrasound went on to have children with RSS. One of the women had also undergone a previous pregnancy termination for fetal anomalies consistent with RSS. The ultrasound findings and details of these 3 cases were reviewed. RESULTS: Both cases of RSS and the third suspected case were found to have nuchal abnormalities on first-trimester scan. All went on to develop malformations consistent with RSS detectable on second-trimester ultrasound. The later 2 cases continued to term and the children had facial characteristics consistent with RSS. CONCLUSION: First-trimester ultrasound assessment of nuchal translucency could be considered as a method for identifying sib recurrences of RSS. In addition, RSS should be on the differential diagnosis when increased nuchal translucency is seen on first-trimester scan.

The use of folic acid for the prevention of neural tube defects and other congenital anomalies.

OBJECTIVE: To provide information regarding the use of folic acid for the prevention of neural tube defects (NTDs) and other congenital anomalies, in order that physicians, midwives, nurses, and other health-care workers can assist in the education of women in the preconception phase of their health care. OPTION: Folic acid supplementation is problematic, since 50% of pregnancies are unplanned and the health status of women may not be optimal. OUTCOMES: Folic acid supplementation has been proven to decrease or minimize specific birth defects. EVIDENCE: A systematic review of the literature, including review and peer-reviewed articles, government publications, the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of March 1993, and statements from the American College of Obstetrics and Gynecology, was used to develop a new clinical practice guideline for the SOGC. VALUES: Peer-review process within the committee structure. BENEFITS, HARMS, AND COSTS: The benefit is reduced lethal and severe morbidity birth defects and the harm is minimal. The personal cost is of vitamin supplementation on a daily basis and eating a healthy diet. RECOMMENDATIONS: 1. Women in the reproductive age group should be advised about the benefits of folic acid supplementation during wellness visits (birth control renewal, Pap testing, yearly examination), especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy nutritional diet, as recommended in Canada's Food Guide to Healthy Eating (good or excellent sources of folic acid: broccoli, spinach, peas, Brussels sprouts, corn, beans, lentils, oranges). (III-A) 3. Women who could become pregnant should be advised to take a multivitamin containing 0.4 mg to 1.0 mg of folic acid daily. (II-1A) 4. Women taking a multivitamin with folic acid supplement should be advised not to take more than 1 daily dose of vitamin supplement, as indicated on the product label. (II-2A) 5. Women in intermediate- to high-risk categories for NTDs (NTD-affected previous pregnancy, family history, insulin-dependent diabetes, epilepsy treatment with valproic acid or carbamazepine) should be advised that high-dose folic acid (4.0 mg-5.0 mg daily) supplementation is recommended. This should be taken as folic acid alone, not in a multivitamin format, due to risk of excessive intake of other vitamins such as vitamin A. (I-A) 6. The choice of a 5 mg folic acid daily dose for women considering a pregnancy should be made under medical supervision after minimizing the risk of undiagnosed vitamin B12 deficiency (hypersegmentation of polymorphonuclear cells, macrocystic indices, large ovalocytes, leukopenia, thrombocytopenia, markedly elevated lactate dehydrogenase level, confirmed red blood cell folate level). (II-2A) 7. Signs or symptoms of vitamin B12 deficiency should be considered before initiating folic acid supplementation of doses greater than 1.0 mg. (III-A) 8. A three-generation pedigree on the families of both the pregnant woman and the biological father should be obtained to identify increased risk for congenital birth defects (i.e., NTD, cardiac, chromosomal, genetic). (III-A) 9. Women who become pregnant should be advised of the availability of noninvasive screening tests and invasive diagnostic tests for congenital birth defects (including NTDs): maternal serum "triple marker screen" at 15 to 20 weeks, ultrasound at 16 to 20 weeks, and amniocentesis after 15 weeks of pregnancy if a positive screening test is present. (I-A) VALIDATION: This is a revision of a previous guideline and information from other consensus reviews from medical and government publications has been used.

Prevention of Rh alloimmunization.

OBJECTIVE: To provide guidelines on use of anti-D prophylaxis to optimize prevention of rhesus (Rh) alloimmunization in Canadian women. OUTCOMES: Decreased incidence of Rh alloimmunization and minimized practice variation with regards to immunoprophylaxis strategies. EVIDENCE: The Cochrane Library and MEDLINE were searched for English-language articles from 1968 to 2001, relating to the prevention of Rh alloimmunization. Search terms included: Rho(D) immune globulin, Rh iso- or allo-immunization, anti-D, anti-Rh, WinRho, Rhogam, and pregnancy. Additional publications were identified from the bibliographies of these articles. All study types were reviewed. Randomized controlled trials were considered evidence of highest quality, followed by cohort studies. Key individual studies on which the principal recommendations are based are referenced. Supporting data for each recommendation is briefly summarized with evaluative comments and referenced. VALUES: The evidence collected was reviewed by the Maternal-Fetal Medicine and Genetics Committees of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: 1. Anti-D Ig 300 microg IM or IV should be given within 72 hours of delivery to a postpartum nonsensitized Rh-negative woman delivering an Rh-positive infant. Additional anti-D Ig may be required for fetomaternal hemorrhage (FMH) greater than 15 mL of fetal red blood cells (about 30 mL of fetal blood). Alternatively, anti-D Ig 120 microg IM or IV may be given within 72 hours of delivery, with testing and additional anti-D Ig given for FMH over 6 mL of fetal red blood cells (12 mL fetal blood). (I-A) 2. If anti-D is not given within 72 hours of delivery or other potentially sensitizing event, anti-D should be given as soon as the need is recognized, for up to 28 days after delivery or other potentially sensitizing event. (III-B) 3. There is poor evidence regarding inclusion or exclusion of routine testing for postpartum FMH, as the cost-benefit of such testing in Rh mothers at risk has not been determined. (III-C) 4. Anti-D Ig 300 microg should be given routinely to all Rh-negative nonsensitized women at 28 weeks' gestation when fetal blood type is unknown or known to be Rh-positive. Alternatively, 2 doses of 100-120 microg may be given (120 microg being the lowest currently available dose in Canada): one at 28 weeks and one at 34 weeks. (I-A) 5. All pregnant women (D-negative or D-positive) should be typed and screened for alloantibodies with an indirect antiglobulin test at the first prenatal visit and again at 28 weeks. (III-C) 6. When paternity is certain, Rh testing of the baby's father may be offered to all Rh-negative pregnant women to eliminate unnecessary blood product administration. (III-C) 7. A woman with "weak D" (also known as Du-positive) should not receive anti-D. (III-D) 8. A repeat antepartum dose of Rh immune globulin is generally not required at 40 weeks, provided that the antepartum injection was given no earlier than 28 weeks' gestation. (III-C) 9. After miscarriage or threatened abortion or induced abortion during the first 12 weeks of gestation, nonsensitized D-negative women should be given a minimum anti-D of 120 microg. After 12 weeks' gestation, they should be given 300 microg. (II-3B) 10. At abortion, blood type and antibody screen should be done unless results of blood type and antibody screen during the pregnancy are available, in which case antibody screening need not be repeated. (III-B) 11. Anti-D should be given to nonsensitized D-negative women following ectopic pregnancy. A minimum of 120 microg should be given before 12 weeks' gestation and 300 microg after 12 weeks' gestation. (III-B) 12. Anti-D should be given to nonsensitized D-negative women following molar pregnancy because of the possibility of partial mole. Anti-D may be withheld if the diagnosis of complete mole is certain. (III-B) 13. At amniocentesis, anti-D 300 microg should be given to nonsensitized D-negativeesis, anti-D 300 microg should be given to nonsensitized D-negative women. (II-3B) 14. Anti-D should be given to nonsensitized D-negative women following chorionic villous sampling, at a minimum dose of 120 microg during the first 12 weeks' gestation, and at a dose of 300 microg after 12 weeks' gestation. (II-B) 15. Following cordocentesis, anti-D Ig 300 microg should be given to nonsensitized D-negative women. (II-3B) 16. Quantitative testing for FMH may be considered following events potentially associated with placental trauma and disruption of the fetomaternal interface (e.g., placental abruption, blunt trauma to the abdomen, cordocentesis, placenta previa with bleeding). There is a substantial risk of FMH over 30 mL with such events, especially with blunt trauma to the abdomen. (III-B) 17. Anti-D 120 microg or 300 microg is recommended in association with testing to quantitate FMH following conditions potentially associated with placental trauma and disruption of the fetomaternal interface (e.g., placental abruption, external cephalic version, blunt trauma to the abdomen, placenta previa with bleeding). If FMH is in excess of the amount covered by the dose given (6 mL or 15 mL fetal RBC), 10 microg additional anti-D should be given for every additional 0.5 mL fetal red blood cells. There is a risk of excess FMH, especially when there has been blunt trauma to the abdomen. (III-B) 18. Verbal or written informed consent must be obtained prior to administration of the blood product Rh immune globulin. (III-C) VALIDATION: These guidelines have been reviewed by the Maternal-Fetal Medicine Committee and the Genetics Committee, with input from the Rh Program of Nova Scotia. Final approval has been given by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada.

RETIRED: Amniocentesis and women with hepatitis B, hepatitis C, or human immunodeficiency virus.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

RETIRED: Cystic fibrosis carrier testing in pregnancy in Canada.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Placental expression of insulin-like growth factor receptor-1 and insulin receptor in the growth-restricted fetal rat.

OBJECTIVE: The type 1 insulin-like growth factor receptor (IGF-R1), which resembles the insulin receptor (INS-R), is expressed abundantly in the placenta. The regulation of fetal growth by IGFs and insulin might reflect their actions on the placenta. This study compared the placental expression of IGF-R1 and INS-R in growth-restricted and normal pregnancies. METHODS: Fetal growth restriction was produced in Sprague-Dawley rats by bilateral ligation of the uterine artery on day 19 (term = 21.5 days). Fetuses were delivered by hysterotomy on day 20, and placental samples were frozen. Fetuses that had been subjected to a sham operation of maternal laparotomy without uterine artery manipulation were studied as matched controls. IGF-R1 and INS-R message was assessed by reverse transcription and polymerase chain reaction amplification of extracted placental RNA. The receptors also were assessed by Western blotting of extracted placental protein. Measurements for the growth-restricted group were expressed as a multiple of that of the matched sham litter. RESULTS: Placental IGF-R1 messenger RNA (mRNA) level was significantly lower in the growth-restricted fetuses (0.66 x sham [0.47-0.93], P <.05), but INS-R mRNA was not different (0.89 x sham [0.63-1.3], P >.5). IGF-R1 protein transcript was similarly reduced in the growth-restricted fetuses (0.78 x sham [0.69-0.88], P <.005), but the INS-R protein transcript was not (0.98 x sham [0.69-1.4], P >.8). Birth weights were significantly less in the growth-restricted group (3.06 +/- 0.07 versus 3.29 +/- 0.06 g, P =.016); placental weights were not (0.54 +/- 0.02 versus 0.54 +/- 0.02 g, P =.90). CONCLUSIONS: The placenta responds to decreased nutrient delivery with decreased expression of IGF-R1. This would reduce the growth-promoting effects of insulin-like growth factors, which include augmentation of placental lactogen production and glucose and amino acid transport. INS-R was unaffected, which suggests that placental response to insulin is less important than its response to insulin-like growth factors in growth restriction.

PREVENTION AND TREATMENT OF VENOUS THROMBOEMBOLISM (VTE) IN OBSTETRICS.

OBJECTIVE: to identify risk factors for venous thromboembolism (VTE) in the peripartum period and to provide guidelines for risk assessment and thromboprophylactic measures for VTE in pregnant women. Guidelines for diagnostic testing and for acute and long term treatment of VTE are also provided.OPTIONS: specific subgroups of pregnant women are defined and appropriate prophylactic measures are outlined. OUTCOMES: venous thromboembolism remains a major cause of morbidity and mortality in pregnancy and the postpartum period. Identification of risk and adequate prophylaxis can decrease the incidence of VTE.EVIDENCE: evidence was gathered using Medline (National Library of Medicine) to identify relevant studies and from bibliographies of articles thus identified.RECOMMENDATIONS: although evidence is lacking to date from Grade I studies (properly controlled randomized studies) in pregnant patients, there is good evidence to support the role of prophylaxis in reducing the incidence of VTE in patients identified to be at risk in the non-pregnant population (II B). Based on risk assessment more patients should be considered for thromboprophylaxis, including women with a past history of a VTE and a known thrombophilia on long-term anticoagulation, women with a past history of a VTE, women with a known thrombophilia who have never experienced a VTE and potentially considered in women at the time of Caesarean section (II B; III C). The occurrence of VTE is effectively reduced by the use of low dose unfractionated heparin. Experience with low molecular weight heparin and pregnancy is building, but is limited at present. Unfractionated heparin remains the standard for the treatment of VTE in pregnancy at the present time. Following initial heparinization for the treatment of VTE, patients should be continued on anticoagulation throughout pregnancy and for six to 12 weeks postpartum or a total of three months of anticoagulation (II A).