Knowledge Of Pregnancy Outcome Research Articles

Fourteen years of the Pregnancy Registry on maternal immunisation with a reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap) vaccine

BackgroundGSK initiated a Pregnancy Registry in the United States (US) for the reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap; Boostrix, GSK) vaccine with the aim to detect and describe pregnancy outcomes in women vaccinated with Boostrix 28 days before estimated conception or during pregnancy. MethodsVoluntary reports of pregnancy exposure to Boostrix received from spontaneous and post-marketing surveillance sources in the US were assessed. Reports were classified as prospective or retrospective based on the knowledge of pregnancy outcomes at the time of reporting. For completeness, reports of exposure to Boostrix or to the Tdap-inactivated poliovirus vaccine (Boostrix-IPV, GSK) reported to the global safety database from countries outside the US were also evaluated. ResultsFrom May 2005 to August 2019, 1517 (1455 prospective and 62 retrospective) pregnancy reports were received in the Boostrix US Pregnancy Registry. Of the prospective reports, 250 had known outcomes: 244 live infants with no apparent birth defects (BDs), three live infants with BDs, and three spontaneous abortions with no apparent BDs. Of the retrospective reports, 55 had known outcomes: 33 live infants with no apparent BDs, 16 live infants with BDs, one spontaneous abortion with no apparent BDs, four stillbirths with no apparent BDs, and one stillbirth with BDs. Cumulatively, 1321 pregnancy reports (1006 for Boostrix; 315 for Boostrix-IPV) were received from countries outside the US. Of these, 163 prospective reports and 551 retrospective reports had known outcomes. Results were in line with those from the Boostrix US Pregnancy Registry. ConclusionsData currently available from the Boostrix US Pregnancy Registry and from countries outside the US suggested that exposure to Boostrix or Boostrix-IPV during pregnancy does not raise safety concerns related to adverse pregnancy outcomes or BDs.

Evaluation of Neural Tube Defects (NTDs) After Exposure to Raltegravir During Pregnancy.

Objective:To evaluate the risk of neural tube defects (NTDs) after exposure to raltegravir during pregnancy.Methods:Exposures to raltegravir during pregnancy reported cumulatively through May 31, 2018, to the company safety database were reviewed to identify cases of NTDs. This database includes all reports of pregnancy from Merck-sponsored clinical trials, spontaneous postmarketing reports, and non-interventional data sources, including the Antiretroviral Pregnancy Registry (APR). Reports were classified as prospective (before knowledge of pregnancy outcome) or retrospective (after knowledge of pregnancy outcome). We also reviewed data from 2 ongoing pregnancy cohorts.Results:A total of 2426 pregnancies with reported outcomes were identified among women exposed to raltegravir: 1238 from the Merck database and 1188 from United Kingdom/Ireland and French pregnancy cohorts. Among all 2426 reports, 1991 were prospective. No cases of NTDs were identified among the prospective pregnancy reports, of which 767 were first trimester, including 456 in the periconception period (at or within 28 days after conception). Among the 435 retrospective reports, 3 NTD cases per APR criteria were identified (anencephaly, and 2 meningomyelocele), of which only one (meningomyelocele) was among exposures in the periconception period. Given the inherent limitations and bias of retrospective reports, it is not appropriate to calculate an incidence rate.Conclusions:Prospectively collected pregnancy outcome data do not suggest an association between raltegravir exposure in the periconception period and NTDs. The current data support the updated DHHS and EACS treatment guidelines for use of raltegravir as a preferred integrase inhibitor in all stages of pregnancy.

Pregnancy Outcomes in Patients with Crohnʼs Disease Treated with Infliximab: Results from the TREATTM Registry

Purpose: The knowledge of pregnancy outcomes in patients with Crohn's disease (CD) receiving antitumor necrosis factor therapy remains limited. Methods: TREAT is an observational registry which evaluates clinical safety outcomes in CD patients treated with infliximab (IFX) and other standards of care in North America. Pregnancy outcomes between July, 1999 and February, 2012 are reported. Results: 6,273 patients were enrolled; 3440 received IFX. At enrollment, IFX-treated patients had a disease duration of 8.4 years, had more severe disease, were more often smokers, and were using more concomitant medication(s) when compared to patients on other CD treatments. A total of 348 pregnancies have been reported in TREAT. Of these, 273 were maternal pregnancies, and 105 occurred in mothers treated with IFX. IFX-treated mothers had higher disease activity during pregnancy: 17.3% had moderate-to-severe disease, 48.0% had mild-to-moderate disease, and 34.7% were in remission, compared to 3.4%, 37.5%, and 58% of the mothers on other CD treatments, respectively. Of the IFX-treated mothers, 33.7% were on AZA/6-MP, and 26.5% were on prednisone during pregnancy, compared to 36.4% and 11.4% of the mothers in the other-treatment-only group. Through an average of 6 years of patient follow-up, 81.6% (80/98) of pregnancies with known outcome in IFX-exposed mothers and 91.0% (81/89) in other-treatments-only exposed mothers resulted in live births (p=0.064). Spontaneous abortions were reported in 16.3% of IFX-treated and 9.0% of the other-treatment-only treated mothers (p=0.134). 92.5% of IFX-exposed and 87.7% of other-treatment-only live births resulted in healthy babies with no defect or other adverse event. One (1.3%) congenital malformation (an ectrodactyly in a familial context) was reported in the IFX-exposed infants, and 3 (3.7%) (a heart murmur associated with a suspicion of cystic fibrosis, a Down's syndrome, and a cortical vision delay) in the other-treatment-only infants. Five (4.8%) IFX-exposed infants were reported to have a prolonged hospital stay, compared to 12 (11.5%) in the other-treatment-only infants. Conclusion: Data from the TREAT registry show that the clinical condition of infants born to women with prenatal exposure to IFX is comparable to those exposed to other CD treatments. A trend for a lower rate of live birth was reported among IFX-exposed mothers, as compared to mothers not exposed to IFX. The confirmation of these results and the role of potential confounding factors, such as high disease activity before or during pregnancy, smoking, and concomitant medication use, will require further study. Disclosure - Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, and Sandborn WJ-Grant/Research Support: Janssen Research and Development, LLC; Langholff W-Employee: Janssen Research and Development, LLC; Morgan J, Nissinen R, Reddy S, Taillard F-All employees Janssen Services, LLC. This research was supported by an industry grant from Janssen Research and Development, LLC.

Antioxidant Vitamins, Long-Chain Fatty Acids, and Spontaneous Preterm Birth

Neither macro- nor micronutrient supplements have been clearly demonstrated to reduce the risk of preterm birth. However, there has been little attention to carotenoids, tocopherols, and long-chain fatty acids other than n-3 polyunsaturates. We conducted a case-control study nested in a large (n = 5337) prospective, multicenter cohort. All cohort women had an interview, examination, and venipuncture at 24-26 weeks' gestation. Frozen plasma samples in spontaneous preterm births (n = 207) and approximately 2-term controls per case (n = 443) were analyzed for carotenoids, retinol, tocopherols, and long-chain fatty acids. Fresh placentas were fixed, stained, and assessed (without knowledge of pregnancy outcome) for histologic evidence of infection or inflammation, decidual vasculopathy, and infarction. High (above the median) plasma concentrations of alpha- and beta-carotene, alpha- and beta-cryptoxanthin, and lycopene were all associated with reductions in risk of spontaneous preterm birth, with evidence of dose-response effects across quartiles. Modest increases in risk were observed with elevated total monounsaturated, total polyunsaturated, and total n-6 polyunsaturated long-chain fatty acids concentrations. Paradoxically, a high gamma-tocopherol concentration was associated with increased preterm birth risk (adjusted odds ratio = 1.8 [95% confidence interval = 1.2-2.6]). Only one of the studied micronutrients (lutein) was independently associated with a reduced risk of decidual vasculopathy (0.5 [0.3-0.9]). Carotenoids and long-chain fatty acids warrant further investigation in in vitro, animal, and human studies of preterm birth.

The Umbilical Coiling Index in Complicated Pregnancy

Coiling is an important property of the umbilical cord and its vessels. The helical arrangement of the umbilical vessels makes the cord both strong and flexible, permitting it to resist external forces that otherwise might compromise blood flow. This study attempted to identify any adverse pregnancy outcomes associated with under- or overcoiling of the umbilical vessels. Coiling was examined in 565 consecutive cases with an indication for histological examination of the placenta. They represented about 10% of all deliveries during the study interval from December 1998 to May 2002. The umbilical coiling index (UCI) was determined as the number of complete coils divided by the length of the umbilical cord in centimeters, as estimated by an observer without knowledge of pregnancy outcomes. Undercoiling was a UCI less than the 10th percentile, and overcoiling, an index above the 90th percentile. Undercoiling of the umbilical cord was found in 18% of cases, and overcoiling in 13.5%. The mean UCI was 0.18, with a standard deviation of 0.12. The UCI was not associated with gestational age at delivery, infant gender maternal age or parity, smoking status, or the presence or absence of preeclampsia, gestational diabetes, or preexisting diabetes. Fetal death, chorioamnionitis, and fetal structural or chromosomal abnormalities were associated with undercoiling. The odds ratio (OR) for fetal death was 4.09, with a 95% confidence interval (CI) of 2.2-7.6. Numerous conditions were associated with overcoiling, including fetal death (OR, 3.7; 95% CI, 1.9-7.4), iatrogenic preterm delivery, an umbilical arterial pH below 7.05, fetal structural or chromosomal abnormalities, thrombosed fetal placental vessels, chronic fetal hypoxia/ischemia, and lower weight for gestational age. Both overcoiling and undercoiling of the umbilical cord vessels are associated with adverse pregnancy outcomes. The investigators propose that the UCI be a routine part of assessing the placenta after delivery. The logical next step is a prospective study to determine the significance of under- and overcoiling of the cord vessels in an unselected population.

Cytomegalovirus (CMV)–EncodedUL144(Truncated Tumor Necrosis Factor Receptor) and Outcome of Congenital CMV Infection

Cytomegalovirus (CMV) is the most common congenital infection in humans. The effect of viral strains on the outcome of congenital CMV is debated. We evaluated whether UL144 polymorphisms in amniotic fluid from CMV-infected Italian women were associated with terminations of pregnancy, subsequent disease in their offspring, or viral load. The study was nested within a prenatal CMV program. We sequenced the UL144 gene from 66 amniotic-fluid samples, without knowledge of pregnancy outcome. We performed data analyses on 56 samples for which all information was available. Genotype C was associated with termination of pregnancy (P=.03). Genotype B was associated with fewer terminations of pregnancy (P=.003). A possible association was found between genotype C and symptomatic disease in newborns (odds ratio, 8.81 [95% confidence interval, 0.48-164.02]; P=.05). There was no association between specific genotype and the viral load in amniotic fluid. Symptomatic newborns who had the most common UL144 genotype (B) were more likely to have higher viral loads than were asymptomatic infants (P=.003). UL144 polymorphisms may be associated with the outcome of congenital CMV infection. Larger studies should be conducted to confirm this association, before genotype analysis can be used, along with other factors, in considering terminations of pregnancy.

The Organization of Teratology Information Services (OTIS) Registry Study

Some population-based studies of the risks of gestational medication use are limited by differential recall or enrollment of mothers of children with abnormalities. Prospective acquisition of exposure information, before knowledge of pregnancy outcome, is the most unbiased manner in which to obtain denominator-based outcome information. The Organization of Teratology Information Services (OTIS) Registry Study will prospectively evaluate pregnancy outcomes in relation to exposures to asthma medications. Patients will be enrolled by participating Teratology Information Services. Information regarding medication exposure, asthma severity, and other important medical events will be assessed during pregnancy by means of standardized interviews, supplemented by medical records. Outcome information will be obtained from copies of the pediatric records. Data analysis will evaluate relative risks of adverse outcomes in exposed compared with unexposed asthmatic and nonasthmatic subjects. (J Allergy Clin Immunol 1999;103:S373-6.)