Patrick Mohide

Sequential pathways of testing after first-trimester screening for trisomy 21

OBJECTIVE: To evaluate the performance and use of second-trimester multiple-marker maternal serum screening for trisomy 21 by women who had previously undergone first-trimester combined screening (nuchal translucency, pregnancy-associated plasma protein A, and free β-hCG), with disclosure of risk estimates. METHODS: In a multicenter, first-trimester screening study sponsored by the National Institute of Child Health and Human Development, multiple-marker maternal serum screening with alpha-fetoprotein, unconjugated estriol, and total hCG was performed in 4,145 (7 with trisomy 21) of 7,392 (9 with trisomy 21) women who were first-trimester screen-negative and 180 (7 with trisomy 21) of 813 (52 with trisomy 21) who were first-trimester screen-positive. Second-trimester risks were calculated using multiples of the median and a standardized risk algorithm with a cutoff risk of 1:270. RESULTS: Among the first-trimester screen-negative cohort, 6 of 7 (86%) trisomy 21 cases were detected by second-trimester multiple-marker maternal serum screening with a false-positive rate of 8.9%. Among the first-trimester screen-positive cohort, all 7 trisomy 21 cases were also detected in the second trimester, albeit with a 38.7% false-positive rate. CONCLUSION: Our data demonstrate that a sequential screening program that provides patients with first-trimester results and offers the option for early invasive testing or additional serum screening in the second trimester can detect 98% of trisomy 21–affected pregnancies. However, such an approach will result in 17% of patients being considered at risk and, hence, potentially having an invasive test. LEVEL OF EVIDENCE: II-2

Late First-Trimester Invasive Prenatal Diagnosis: Results of an International Randomized Trial

OBJECTIVE: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11–14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. METHODS: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. RESULTS: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P = .07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P = .02) overall and in week 13 (P = .03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. CONCLUSION: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. LEVEL OF EVIDENCE: I

Late first-trimester placental disruption and subsequent gestational hypertension/preeclampsia.

OBJECTIVE: To evaluate the potential relationship between placental disruption in weeks 13 and 14 and the subsequent development of gestational hypertension or preeclampsia. METHODS: Using subjects recruited during a randomized trial funded by the National Institute of Child Health and Human Development, which compared early amniocentesis and late transabdominal chorionic villus sampling (CVS) in weeks 13 and 14, rates of gestational hypertension and preeclampsia were compared between cases with varying degrees of placental disruption. RESULTS: A total of 3,698 of 3,775 randomized subjects had cytogenetically normal pregnancies and were analyzed. A significantly higher rate of hypertension/preeclampsia was observed in the late CVS group (5.4%, n = 1,878) compared with the early amniocentesis cohort (3.5%, n = 1,820; P = .005). This difference persisted after controlling for maternal age, body mass index, parity, previous preterm delivery, smoking, and fetal gender. Early amniocentesis cases were further stratified on the basis of whether the placenta had been penetrated (n = 460) or not (n = 1,360). Risk of hypertensive complications was lowest if the placenta was not traversed (3.4%), greater with placental penetration (3.9%), and highest when the placenta was directly sampled during CVS (5.4%, P = .02). CONCLUSION: We hypothesize that focal disruption of the placenta at 13–14 weeks may increase the risk of hypertension/preeclampsia. These findings provide support for the theory that disturbances in early placentation lead subsequently to maternal hypertension. LEVEL OF EVIDENCE: II-1

Health-related quality-of-life assessment of prenatal diagnosis: chorionic villi sampling and amniocentesis.

This study assesses the health-related quality-of-life (HRQL) effects of chorionic villi sampling (CVS) and genetic amniocentesis (GA), including both process and outcomes of prenatal diagnosis. The HRQL of 126 women participating in a randomized controlled clinical trial of CVS versus GA in Toronto and Hamilton, Ontario, was assessed in four interviews at weeks 8, 13, 18, and 22 of pregnancy. Statistical analyses included analysis of variance, repeated measures analysis of covariance, chi-square, Fishers exact test, Students t-tests, and paired t-tests. Utility scores for patients undergoing CVS exceeded those for GA patients at week 18 (p = 0.04). Utility scores for hypothetical health states did not differ significantly by trial arm. CVS results in slightly improved HRQL during prenatal diagnosis. This advantage needs to be weighed against the high disutility patients attach to infrequent outcomes associated with pregnancy losses, equivocal diagnoses, and diagnostic inaccuracy.

Women's perception of self-worth and access to health care.

Objective: Research has shown differences in health status and health care utilization related to culture, economic status, and health care development. This paper reports on a study comparing attitudes of women in three countries, at various stages of development, about their own health and self‐worth and asks if these differences account for differences in health care utilization and inequities in health status. Method: A questionnaire, administered to 100 women in each of Yemen, Uganda and Canada, explored womens perception of their own health and health care seeking behavior. Result: Womens perception of themselves as worthy of care was positively related to utilization. The ability to make ones own health care decisions varied with her countrys development level. Implementation strategies must consider womens decision‐making capacity. Conclusion: To achieve improved health status, policies and programs must commit to encouraging appropriate social and cultural changes, using a ‘cross‐sectoral approach’, involving both gender and development issues.

Multiple congenital anomalies in a fetus with 45,X/46,X,r(X)(p11.22q12) mosaicism

Ring X chromosomes that do not undergo inactivation may cause malformations and mental retardation. We report on a fetus with anencephaly, total dorsal rachischisis, and diaphragmatic hernia that was found to have a mosaic 45,X/46,X,r(X)(p11.22q12) karyotype. Fluorescent in situ hybridization (FISH) confirmed that the ring chromosome was X-derived. This report expands the phenotypic spectrum of mosaic monosomy X and small ring X chromosomes.

Excision of lambda prophage: effects on host survival.

Induction with ultraviolet light of K12 lysogens carrying defective prophages leads to death of the host cell. In order to determine whether the killing accompanying induction was due to diffusible phage products, or was a result of prophage excision itself, the survival of lysogens carrying DNA defective prophages on an extra chromosomal site (the F-gal episome), were examined. Induction of prophages, carrying mutations in the x region, or the N, O or P cistrons, from this location, did not result in host death, but, with the exception of mutants in the x region of the lambda chromosome, it did result in loss of the episome. On the basis of these results, it is proposed that the lethal event in induction of the DNA-defective mutants is due to prophage excision, which leads to interruption of the host chromosome, and cell death.

Prospective cohort study of three- versus two-dimensional ultrasound for prediction of oocyte maturity

OBJECTIVE To determine whether three-dimensional follicular ultrasound (3-D) measurements are better predictors of optimal timing of hCG administration than two-dimensional (2-D) images, the current standard. DESIGN Prospective, cohort study. SETTING Tertiary referral center. PATIENT(S) Seventy-six patients undergoing IVF. INTERVENTION(S) Seventy-six consecutive patients undergoing serial follicular monitoring during IVF had an additional daily 3-D volume scan of their ovaries once lead follicles had reached 16 mm diameter. MAIN OUTCOME MEASURE(S) Number of mature oocytes retrieved. RESULT(S) The 2-D follicular diameter measurements predicted 25.4% of the observed variance in the number of mature oocytes retrieved. The 3-D follicular volume measurements were more predictive of outcome, accounting for 29.2% of the observed variance in number of mature oocytes retrieved. Follicles >22 mm diameter and 5 mL volume were associated with fewer mature oocytes reflecting an undesired postmature state. Follicles measuring 11 to 15 mm had a 50% chance of yielding a mature oocyte. CONCLUSION(S) Three-dimensional follicular volume measurements have a stronger correlation with the number of mature oocytes retrieved than 2-D measurements. As 3-D technology improves, this parameter may replace 2-D measurements in the optimal timing of hCG before oocyte retrieval.

Amniotic fluid lipase in two cases of duodenal obstruction

within the female pelvic organs is presented. Review of the literature revealed only one case similar to this with traumatic tear of the posterior leaf of the broad ligament coupled with splenic capsular rupture in a sixweek gestation reported by Ogunbode and assodates.2 Many instances of splenic rupture alone previously have been reported when the preoperative diagnosis was hemoperitoneum secondary to rupture of a pelvic organ. The lack of pathologic evidence of chorionic villi in our case can only be explained by rupture at the site of placentation so complete as to remove all placental tissue from the remaining Fallopian tube. The history of amenorrhea, morning nausea, breast tenderness, and urinary frequency in a sexually active woman using no contraception offers presumptive evidence of an early pregnancy. Rupture of a tuboovarian abscess is an alternative explanation but the absence of pus makes this less likely. The corpus luteum on the left ovary was intact, ruling out bleeding from this source. Splenic capsular rupture was likely traumatic as a result of the fall during the hypotensive period. One objective of this presentation is to focus once again on this uncommon phenomenon. As evidenced in our case report, if one’s findings are inconsistent with the clinical picture in cases of intra-abdominal hemorrhage, the possibility of rupture high in the abdomen, namely, the spleen, must be considered and sought.

Practice patterns and attitudes toward education among Canadian obstetricians and gynecologists

A group of 1370 specialists in obstetrics and gynecology were surveyed for information about practice patterns, continuing medical education preferences, and their perception of the adequacy of their own residency training. The overall response rate was 65.7%. More than half were in solo practice, practiced in communities of over 250,000, had been in practice for more than 10 years, or had a full or part-time appointment with a Canadian medical school. A wide range of continuing medical education methods were used. Journals were ranked highest by 41%. It is disturbing that very few physicians (15%) indicated any involvement in practice audit. The quality of residency training was ranked low in a number of areas including genetic counseling, ultrasound, neonatology, intensive care, colposcopy, sexual dysfunction, marital counseling, and hysteroscopy. The survey highlights a number of areas that merit the attention of Canadian programs in postgraduate and continuing medical education in obstetrics and gynecology.