Olufemi Olatunbosun

Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes

Background: In previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy. Methods: We used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents. Results: We included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole–trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39–1.66), severe preeclampsia (OR 1.77, 95% CI 1.38–2.28), placental abruption (OR 1.32, 95% CI 1.12–1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01–1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11–1.34) and fetal death (OR 1.35, 95% CI 1.07–1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results. Interpretation: Maternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.

A Randomized Controlled Trial of Outpatient Versus Inpatient Labour Induction with Vaginal Controlled-Release Prostaglandin-E2: Effectiveness and Satisfaction

BACKGROUND Outpatient management in obstetrics is expanding, but evidence to support outpatient labour induction is needed. OBJECTIVE To compare the effectiveness, acceptability, duration of hospitalization, and safety of outpatient and inpatient induction of labour with intravaginal controlled-release prosta-glandin-E2 (CR-PGE2). METHODS A prospective, randomized, controlled trial enrolled 300 women at term with parity < or = 5 and singleton pregnancies in cephalic presentation. Each had an unscarred uterus, a normal non-stress test (NST), and a Bishop score of < or = 6. After insertion of the CR-PGE2, and 1 hour of monitoring, those in the outpatient group were discharged home, to return with onset of labour or 12 hours later for an NST. If not already in labour 24 hours later, the women returned for inpatient induction. Vaginal examination was not repeated before 24 hours unless the patient was contracting and required analgesia. Inpatients remained on the antepartum ward but were otherwise treated similarly. The women in both groups reported ratings of satisfaction, pain, and anxiety over the telephone until they were in labour. RESULTS There were 150 women randomized to outpatient and 150 women to inpatient induction of labour. The number of women who were in labour or who delivered by 24 hours in the outpatient group was 115 (0.77, 95% confidence interval [CI] 0.70-0.84) and in the inpatient group was 107 (0.72, 95% CI 0.64-0.79). The median times to labour were 9.8 hours (95% CI, 8.1-11.4) and 11.4 hours (95% CI, 10.1-12.7), and to delivery were 21.4 hours (95% CI, 19.2-23.5) and 20.7 hours (95% CI, 18.4-23.0), for the outpatient and inpatient groups, respectively. In the outpatient group, 56% of women reported high satisfaction during the initial 12 hours of induction compared to 39% in the inpatient group (p < 0.008). Ratings of pain and anxiety during the first 12 hours of induction were similar. In the outpatient group, women were at home for a median of 8 hours (95% CI, 6.7-9.4) before labour and delivery. There were no significant differences in adverse outcomes. CONCLUSIONS This study suggests that outpatient induction of labour with intravaginal CR-PGE2 may be a reasonable option for selected low-risk women; however, further study is needed to confirm the safety of this approach.

Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: A randomized clinical trial

We determined the effects of 2 years of exercise training and soy isoflavone supplementation on bone mass and lipids in postmenopausal women provided with calcium and vitamin D. Women were randomized to four groups: exercise training (Ex); isoflavone supplementation (Iso: 165 mg/d [105 mg/d aglycone equivalent]); combined Ex and Iso (ExIso); and placebo (control). Exercise included resistance training (2 days/week) and walking (4 days/week). Our primary outcomes were lumbar spine and hip bone mineral density (BMD). Secondary outcomes included hip geometry, tibia and radius speed of sound (SOS), dynamic balance (6 m backward tandem walking), blood lipids, mammography, and endometrial thickness. A total of 351 women (Ex = 86, Iso = 90, ExIso = 87, control = 88) were randomized, with 298 analyzed at 2 years (Ex = 77, Iso = 76, ExIso = 72, control = 73). There was a significant interaction for total hip BMD (p < 0.001) such that ExIso had a greater rate of decrease (absolute change [95% confidence interval] = −0.018 [−0.024, −0.012] g/cm2) than either the Ex or Iso groups alone (−0.005 [−0.01, 0.001] and −0.005 [−0.011, 0.001] g/cm2, respectively). There were no differences between groups for changes in lumbar spine BMD and minimal significant changes in hip geometric properties and bone SOS. Exercise groups improved dynamic balance as measured by a decrease in backward tandem walking time over 6 m (p = 0.017). Isoflavone groups decreased low density lipoproteins (Iso: −0.20 [−0.37, −0.02] mmol/L; ExIso: −0.23 [−0.40, −0.06] mmol/L; p = 0.003) compared to non‐isoflavone groups (Ex: 0.01 [−0.16, 0.18] mmol/L; control: −0.09 [−0.27, 0.08] mmol/L) and had lower adverse reports of menopausal symptoms (14% versus 33%; p = 0.01) compared to non‐isoflavone groups. Isoflavone supplementation did not increase endometrial thickness or abnormal mammograms. We conclude exercise training and isoflavone supplementation maintain hip BMD compared to control, but these two interventions interfere with each other when combined. Isoflavone supplementation decreased LDL and adverse events related to menopausal symptoms.

Maternal characteristics associated with pregnancy exposure to FDA category C, D, and X drugs in a Canadian population

To estimate the frequency of exposure to prescription Food and Drug Administration (FDA) category C, D, and X drugs in pregnant women, and to analyze the maternal characteristics associated with such an exposure.

Patterns of pregnancy exposure to prescription FDA C, D and X drugs in a Canadian population

Objective:To examine prescription Food and Drug Administration (FDA) C, D and X drugs in general obstetric population.Study Design:Historical cohort study.Result:A total of 18 575 women who gave a birth in Saskatchewan between January 1997 and December 2000 were included. Among them, 3604 (19.4%) received FDA C, D or X drugs at least once during pregnancy. The pregnancy exposure rates were 15.8, 5.2 and 3.9%, respectively, for category C, D and X drugs, and were 11.2, 7.3 and 8.2%, respectively, in the first, second and third trimesters. Salbutamol (albuterol), trimethoprim/sulfamethoxazole (co-trimoxazole), ibuprofen, naproxen and oral contraceptives were the most common C, D, X drugs used during pregnancy.Conclusion:About one in every five women uses FDA C, D and X drugs at least once during pregnancy, and the most common prescription drugs in pregnancy are antiasthmatic, antibiotics, nonsteroid anti-inflammation drugs, antianxiety or antidepressants and oral contraceptives.

Ultrasound image attributes of human ovarian dominant follicles during natural and oral contraceptive cycles

BackgroundComputer-assisted analyses were used to examine ultrasound image attributes of human dominant ovarian follicles that developed during natural and oral contraceptive (OC) cycles. We hypothesized that image attributes of natural cycle follicles would quantitatively differ from those in OC cycles and that OC cycle follicles would possess image attributes indicative of atresia.MethodsDominant ovarian follicles of 18 clinically normal women were compared using transvaginal ultrasonography for the 7 days before ovulation during a natural cycle (n = 9) or the 7 days before peak estradiol in women using OC (n = 11). Follicles were analyzed using region and line techniques designed to compare the image attributes numerical pixel value (NPV), pixel heterogeneity (PH) and area under the curve (AUC).ResultsNPV was higher in OC cycle follicles with region analysis and tended to be higher with line analysis (p = 0.005 and p = 0.06, respectively). No differences were observed in two other image attributes (AUC and PH), measured with either technique, between natural and OC cycle follicles.ConclusionThe increased NPV value of OC cycle follicles and lack of differences in PH and AUC values between natural cycle and OC cycle follicles did not support the hypothesis that OC cycle follicles would show ultrasonographically detectable signs of atresia. Image attributes observed in OC cycle follicles were not clearly indicative of atresia nor were they large enough to preclude preovulatory physiologic status in OC cycle follicles.

Human papillomavirus vaccine, teen sex and politics

Infection with human papillomavirus (HPV) is a major risk factor for cervical cancer. The development of a safe and effective vaccine against HPV and its routine administration promises to be a major breakthrough in efforts at cervical cancer prevention. Research indicates that optimum benefit from the vaccine would be achieved in pre-adolescents to ensure protection against this sexually transmitted virus before sexual activity is initiated. The vaccine would probably be targeted primarily at girls but could also be used on boys to limit the spread of the virus thereby providing an excellent example of male involvement in reproductive health. It is rather unfortunate that even before the vaccine becomes available commercially and introduced into service delivery opposition is growing toward its widespread application. (excerpt)

Transvaginal Sonography and Fiberoptic Illumination of Uterine Vessels for Abdominal Cervicoisthmic Cerclage

BACKGROUND Transabdominal cervicoisthmic cerclage is a procedure carried out to increase the fetal salvage rates in women who are poor candidates for the more usual procedure of transvaginal cerclage or for those with previously failed vaginal procedures. Although several modifications have been applied to the original procedure in an attempt to reduce the morbidity, bleeding arising from trauma to the uterine vessels during suture placement remains problematic. CASE Our technique involves transilluminating the uterine vessels during placement of the 5-mm-wide Mersilene (Ethicon Inc., Peterborough, Ontario, Canada) tape suture through an avascular space above the junction of the cervix and the uterine isthmus. This obviates the need to dissect or tunnel into the broad ligament. Simultaneous intraoperative transvaginal ultrasonography is used to enhance high suture placement at the isthmus and monitor the fetoplacental unit. We have used this technique in a series of five women with cervical incompetence for seven pregnancies. All but one procedure resulted in live term births. There were no major complications. CONCLUSION Simultaneous intraoperative ultrasonography and uterine vessel transillumination simplified suture placement during abdominal cerclage, and reduced the amount of dissection and bleeding.

Curriculum reform for reproductive health.

A new model of reproductive health care delivery is unfolding, driven by emerging health issues, expanding technology and increasing public expectations. Additional imperatives in service provision for womens health compel reforms to undergraduate medical education using reproductive health as the basis for restructuring curriculum contents. These developments provide an opportunity for implementing the recommendations from various international conferences through continuing professional development and an evidence-based approach to clinical decision-making. A three-pronged approach based on reproductive health, problem-based learning and evidence-based medicine, has much potential for improving subsequent clinical practice and the overall reproductive health of the community. Appropriate changes to existing curricula will facilitate integration of the principles of reproductive health and the new philosophy of doctor-patient relationship into clinical supervision and training of students.

Androgen Replacement Therapy and Women’s Health

Abstract Although androgen replacement has been in use for several decades for various gynaecological disorders, it has had few adherents in womens health because of misconceptions that it is unphysiobgical and a male hormone. The potential role of androgens in the pharmacological management of menopausal hormone deficiency states remains to be firmly defined, but there has recently been renewed interest in the addition of low-dose androgen to the traditional estrogen replacement therapy. This is a welcome development because not all menopausal symptoms are adequately controlled with estrogen or estrogen/progestin therapy. Weight gain, increase in body hair and slight enlargement of the clitoris constitute the most important side effects experienced by androgen users. The purpose of this review is to discuss the role of androgens as an adjuvant to estrogen/progestin replacement therapy with the hope that the clinician will evaluate its incorporation into menopausal womens health care.