Rate Of Elective Termination Research Articles

Estimating cumulative incidence functions in competing risks data with dependent left-truncation.

Both delayed study entry (left-truncation) and competing risks are common phenomena in observational time-to-event studies. For example, in studies conducted by Teratology Information Services (TIS) on adverse drug reactions during pregnancy, the natural time scale is gestational age, but women enter the study after time origin and upon contact with the service. Competing risks are present, because an elective termination may be precluded by a spontaneous abortion. If left-truncation is entirely random, the Aalen-Johansen estimator is the canonical estimator of the cumulative incidence functions of the competing events. If the assumption of random left-truncation is in doubt, we propose a new semiparametric estimator of the cumulative incidence function. The dependence between entry time and time-to-event is modeled using a cause-specific Cox proportional hazards model and the marginal (unconditional) estimates are derived via inverse probability weighting arguments. We apply the new estimator to data about coumarin usage during pregnancy. Here, the concern is that the cause-specific hazard of experiencing an induced abortion may depend on the time when seeking advice by a TIS, which also is the time of left-truncation or study entry. While the aims of counseling by a TIS are to reduce the rate of elective terminations based on irrational overestimation of drug risks and to lead to better and safer medical treatment of maternal disease, it is conceivable that women considering an induced abortion are more likely to seek counseling. The new estimator is also evaluated in extensive simulation studies and found preferable compared to the Aalen-Johansen estimator in non-misspecified scenarios and to at least provide for a sensitivity analysis otherwise.

Birth outcomes after inadvertent use of category X drugs contraindicated in pregnancy: Where is the real risk?

Öztürk Z, Ölmez E, Gürpınar T, Vural K. Birth outcomes after inadvertent use of category X drugs contraindicated in pregnancy: Where is the real risk? Turk J Pediatr 2018; 60: 298-305. Drugs contraindicated in pregnancy are medicines that should be avoided by pregnant women, since they carry a concern for teratogenicity or there is no indication for their use during pregnancy. It does not mean that exposures to these drugs always cause harm. The aim of the present study was to investigate the risk of adverse outcomes following maternal exposure to the drugs contraindicated in pregnancy. We retrospectively analyzed prenatal drug exposure records of the pregnant patients referred to the clinical pharmacology consultation service in a tertiary-level university hospital from January 2007 until December 2012. Exposures to category X drugs (CXD) contraindicated in pregnancy were evaluated. After the expected date of delivery, we collected data about pregnancy complications and the outcomes. For comparison the women in the exposed group (N=52) were matched with a control group (N=162) of pregnant women without teratogenic exposure. We observed only one baby born with a birth defect (congenital cryptorchidism) in CXD group (2.6%) and four in control group (RR 0.91; 95% CI 0.10- 7.94). The rates of adverse pregnancy outcomes including miscarriage, preterm birth and congenital abnormality were not significantly different from controls. However, the rate of elective termination of pregnancy was higher in women exposed to CXD while pregnant (RR 2.54; 95% CI 1.11- 5.80, p = 0.027). Contraceptive failure and unintended pregnancy are the reasons for inadvertent drug exposure and choosing abortion. The high perception of teratogenic risk among pregnant women may cause terminations of pregnancies. Individual risk assessment and avoiding the phrase `CXD` or `contraindicated in pregnancy` in counseling may help to reduce maternal concerns about medication use in pregnancy.

Pregnancy Outcome Following Exposure to Topical Retinoids: A Multicenter Prospective Study

Concerns have been raised about the use of topical retinoids since the publication of isolated cases of characteristic retinoid embryopathy, originally described after oral use. A collaborative study of the European Network of Teratology Information Services was carried out to evaluate the rate of congenital malformations following first-trimester topical retinoid exposure. A population of 235 exposed pregnant women was compared with 444 controls. No significant differences were observed between groups with regard to the rates of spontaneous abortion (odds ratio [95% confidence interval], 1.5 [0.8-2.7]), minor birth defects (1.3 [0.4-3.7]), and major birth defects (1.8 [0.6-5.4]). No child showed features of retinoid embryopathy. The rate of elective termination in the exposed group was increased 3-fold (3.4 [1.5-7.8]). In conclusion, these results do not suggest an increased risk of retinoid embryopathy. However, according to current knowledge, topical retinoids cannot be advised for use during pregnancy because their risk/benefit ratio remains questionable.

Pregnancy outcome after paternal exposure to azathioprine/6-mercaptopurine

There are only few studies with conflicting results on pregnancy outcome after paternal exposure to azathioprine or 6-mercaptopurine. In our study, pregnancy outcome of 115 prospectively followed pregnancies after paternal exposure to azathioprine or 6-mercaptopurine is compared to a control group of 341 pregnancies. The rate of major malformations was not increased (3.0% in exposed versus 2.2% in the control group). There was no specific pattern of birth defects and no indication for chromosomal aberrations in the exposed group. We observed a higher rate of elective terminations of pregnancy in the exposed group and a non-significant increase of spontaneous abortions (cumulative incidence 19% versus 13%, respectively). Further prospective studies are required to address the question of a possibly increased risk for spontaneous abortion.

Truncus Arteriosus: Diagnostic Accuracy, Outcomes, and Impact of Prenatal Diagnosis

Limited data exist on the impact of prenatal diagnosis and outcomes of fetal truncus arteriosus (TA). We sought to assess prenatal diagnostic accuracy and prenatal outcomes in fetuses with TA and compare postnatal outcomes in neonates with prenatally and postnatally diagnosed TA. Records were reviewed for patients diagnosed with TA in utero or at <or=60 days of life from 1992 to 2007. Forty-three (32%) of 136 TA patients had prenatal diagnosis. Five patients with TA were prenatally misdiagnosed, and 5 with other congenital heart diseases were misdiagnosed with TA prenatally. Of 28 fetuses diagnosed at <24 weeks gestation, 19 (68%) did not survive to birth because of spontaneous fetal death (n = 2) or because of elective termination (n = 17). Pregnancy termination was not more likely for fetuses with extracardiac anomalies. Of 19 live-born patients with correct prenatal diagnosis of TA, 2 (11%) died before surgery, and 4 (24%) died in the early postoperative period. All patients who died presurgically had been diagnosed prenatally. Overall, early postoperative mortality was 10%. Prenatal diagnosis of TA remains challenging and is associated with a high rate of elective termination. Fetal diagnosis was associated with younger age at repair but was not associated with improved neonatal survival.

Pregnancy outcome after gestational exposure to the new macrolides: A prospective multi-center observational study

Objectives To determine whether the use of the new macrolides (azithromycin, clarithromycin, roxithromycin) during the first trimester of pregnancy is associated with an increased risk of major malformations. Study design In a prospective multi-center study, pregnancy outcome was compared between pregnant women exposed to one of the new macrolides during the first trimester of pregnancy and two comparison groups one exposed to other antibiotics and the other to other non-teratogenic medications. All women enrolled in the study called one of the three participating teratogen information services (TIS). Group 1 macrolides ( n = 161), group 2 other antibiotics ( n = 213) and group 3 non-teratogens ( n = 740). Results A total of 161 women exposed to the new macrolides (118 were exposed in the first trimester of pregnancy) and 953 from a comparison groups were followed up. The rate of major malformations in the study group was 4.1% compared to 2.1% in the other antibiotics exposed group (OR = 1.41, 95% CI 0.47–4.23) and 3.0% in the non-teratogens exposed group. The rate of elective terminations of pregnancy was significantly higher in the exposed group in compare to both comparison groups. Conclusion Our study, although relatively small sized, suggests that the use of the new macrolides during the first trimester of pregnancy does not represent an increased risk for congenital malformations strong enough for an induced abortion after such an exposure. Elective terminations of pregnancy because of early exposure to these medications should be reconsidered.

Pregnancy outcome following non-obstetric surgical intervention

Objective To evaluate the effects of non-obstetric surgical procedures on maternal and fetal outcome. Methods A systematic review of all English language literature. Results Fifty-four papers met the inclusion criteria. The overall number of patients reported was 12,452. Reported maternal death was rare at .006%. The miscarriage rate was 5.8%; however, this number is difficult to interpret since matched controls were not available. The rate of elective termination of pregnancy following non-obstetric surgery was 1.3%. The rate of premature labor induced by non-obstetric surgical intervention was 3.5% and this was noted specifically following appendectomy versus other types of interventions ( P < .001). A total of 2.5% of pregnancies resulted in fetal loss. The prematurity rate was 8.2%. The rate of major birth defects among women who underwent non-obstetric surgical intervention in the first trimester was 3.9%. Sub-analysis of papers reporting on appendectomy during pregnancy revealed a high rate (4.6%) of surgery-induced labor. Fetal loss associated with appendectomy was 2.6%; however, this rate was increased when peritonitis was present (10.9%). Conclusions Modern surgical and anesthesia techniques appear to diminish the rate of maternal death. Surgery in the first trimester does not appear to increase major birth defects and should not be delayed when indicated. Acute appendicitis with peritonitis is associated with higher risk to the mother and fetus.

Safety of Haloperidol and Penfluridol in Pregnancy

To assess the safety of the butyrophenone neuroleptics haloperidol and penfluridol in pregnancy. The rate of major anomalies was compared between a cohort of pregnant women counseled for gestational exposure to haloperidol or penfluridol and a control group counseled for nonteratogen exposure. This multicenter, prospective, controlled study was conducted within the European Network of Teratology Information Services (ENTIS) and included women who contacted 1 of 4 teratology information services for counseling between January 1989 and December 2001. We followed up on the outcomes of 215 pregnancies exposed to haloperidol (N = 188) or penfluridol (N = 27)-78.2% (of 206) were in the first trimester-and compared to outcomes of 631 ENTIS controls. The rate of congenital anomalies did not differ between the haloperidol/penfluridol-exposed group and the control group (6/179 = 3.4% vs. 22/581 = 3.8%, p = .787). No difference was found by limiting the analysis to those exposed to butyrophenones during the first trimester. There were 2 cases of limb defects in the butyrophenone-exposed group (1 after haloperidol and 1 after penfluridol exposure) and none in the controls. A higher rate of elective terminations of pregnancy (8.8% vs. 3.8%, p = .004), a higher rate of preterm birth (13.9% vs. 6.9%, p = .006), a lower median birth weight (3155 g vs. 3370 g, p < .001), and a lower median birth weight of full-term infants (3250 g vs. 3415 g, p = .004) were found in the butyrophenone-exposed group compared to the controls. This study suggests that haloperidol and penfluridol do not represent a major teratogenic risk. Since a possible association between butyrophenone exposure and limb defects cannot be ruled out with this sample size, a level II ultrasound with emphasis on the limbs should be considered in pregnancies with first trimester exposure.

Nihilism in the 1990s: the true mortality of congenital diaphragmatic hernia.

Reported survival in congenital diaphragmatic hernia (CDH) fails to allow for case selection bias. This study reports the incidence of CDH in a geographically defined population over 11 years and assesses the effect of new therapies (high-frequency oscillatory ventilation, extracorporeal membrane oxygenation, inhaled nitric oxide, and delayed surgery) on survival when case selection is avoided. A retrospective review of cases from a regional case registry, the Northern Region Congenital Anomaly Survey, was conducted. A total of 185 cases were identified. Mortality was 62% and did not vary significantly during the study period. Mortality was unaffected by the introduction of new therapies. There was a significant inverse correlation between the rate of elective termination and survival of live borns. The presence of an additional anomaly increased mortality to 79%. The mortality of CDH when complete case ascertainment is achieved is unaffected by new therapies. The survival rate is principally determined by the rate of antenatal termination and the incidence of associated anomalies. Reports of improved survival of CDH should be interpreted with caution, as variations in outcome are more likely to be explained by case selection artifact.

Pregnancy outcome after gestational exposure to mebendazole: A prospective controlled cohort study

Objective: Mebendazole is an anthelmintic that is commonly needed in women of reproductive age. Its use in pregnancy is a reason for concern for women and their health care providers. The purpose of this study was to examine the fetal safety of mebendazole. Study Design: The Israeli Teratogen Information Service prospectively collected and followed 192 pregnancies exposed to mebendazole in pregnancy, 71.5% of whom had first-trimester exposure. Pregnancy outcome was compared with that of a matched control group, who were counseled for nonteratogenic exposure. Results: There was no increase in the rate of major malformations between the groups (5/150 pregnancies [3.3%; mebendazole] vs 3/175 pregnancies [1.7%; nonteratogenic control subjects]; P = .478). There was a higher rate of elective terminations of pregnancy in the exposed group compared with the control group (22/192 pregnancies [11.5%; mebendazole] vs 3/192 pregnancies [1.6% [nonteratogenic control subjects]; P = .000). Conclusion: This study suggests that mebendazole does not represent a major teratogenic risk in humans when it is used in the doses that are used commonly for pinworm (Enterobius vermicularis) infestation. (Am J Obstet Gynecol 2003;188:282-5.)

The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study

Objectives: The purpose of the Eurofetus Study was to evaluate the accuracy of the antenatal detection of malformations by routine ultrasonographic examination in unselected populations. Study Design: All ultrasonographic diagnoses of malformations and the outcomes of the fetuses were prospectively recorded in 61 European obstetric units over a 3-year period (1990-1993). Also recorded were all cases of malformation diagnosed after abortion or birth for the mothers who underwent follow-up in these centers. Results: Of 3685 malformed fetuses, 2262 had received diagnoses during pregnancy (sensitivity, 61.4%). Of a total number of 4615 malformations, 2593 were detected (sensitivity, 56.2%). The detection sensitivity was higher for the major than for the minor abnormalities (73.7% vs 45.7%), and the diagnosis was made earlier in the pregnancy (24.2 weeks vs 27.6, P < .01). Overall, 55% of the major abnormalities were detected within 24 gestational weeks. Within each severity group the accuracy of detection depended on the system. For the major abnormalities it was better for the central nervous system (88.3%) and urinary tract (84.8%) but lower for the heart and great vessels (38.8%). Detection of minor abnormalities was also effective for the urinary tract (89.1%) but not for the heart and great vessels (20.8%) or the musculoskeletal system (18%). Detection of abnormalities had an influence on the rate of termination of pregnancy. The rate of live births for the mothers bearing fetuses with major abnormalities was lower than that for the mothers in whom no abnormalities were detected, mainly because of the higher rate of elective terminations of pregnancy in the former group. Conclusion: Systematic ultrasonographic screening during pregnancy can now detect a large proportion of fetal malformations, although some still escape detection. (Am J Obstet Gynecol 1999;181:446-54.)