Abstract

Phenylketonuria is an autosomal recessive disorder caused by a deficiency in phenylalanine hydroxylase enzyme.  Infants with PKU are normal but if not treated they have an intellectual disability since elevated phenylalanine levels are neurotoxic.  Nutritional treatment is limiting natural dietary protein and treating with phenylalanine free protein from specially formulated medical foods. . Early and lifelong maintenance of blood phenylalanine levels of less than 360 µmol/L is recommended. Most patients with PKU are are unsuccessful in following the stringent  dietary restrictions as adults and adolescents that are required. Pregnant females with PKU are at high risk for the embryopathy of maternal PKU syndrome if they did not maintain phenylalanine levels in the recommended range from conception throughout pregnancy.  Features of maternal PKU include intrauterine growth restriction, and increased frequency of spontaneous abortions, microcephaly, congenital heart disease, and a moderate to severe intellectual disability.

Pegvaliase is a subcutaneously administered PEGlated recombinant phenylalanine ammonia lyase enzyme that was approved in 2018.  Pegvaliase was not initially studied in pregnant females but since approval multiple successful pregnancies have been reported.  We have treated 3 pregnancies with pegvaliase successfully with normal outcomes.  These women were unable to maintain phenylalanine levels in the desired range with medical food.  With enzyme therapy they were able to maintain phenylalanine levels in the desired range.  Given with PKU who desired pregnancy were advised to protect from pregnancy until phenylalanine levels were within the desired range and checked blood phenylalanine levels every 1 to 2 weeks throughout the pregnancy.  Pegvaliase dose and diet adjustments were made as needed.

ABSTRACT

Background and aim: The suppression of the ovaries could be related to COVID-19, as they are often suppressed in acute illnesses to ensure the normal functioning of other systems and organs. In this context, some patients with COVID-19 were found to have inappropriately high levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [1,2]. In the immune response against SARS-CoV-2, interleukin-6 is released along with other cytokines such as interleukin-8 and tumor necrosis factor alpha, which trigger a pro-coagulant state that is unfavorable for the blastocyst or fetus in a normal human uterus. In addition, high rates of antiphospholipid antibodies (aPLs)  have been found in severe COVID-19 patients, although their association with intrahospital vascular thrombosis or worse outcome was not clearly proven [3], and also in patients with subsequent post-COVID syndrome, which could affect pregnancy and fertility. For diagnosis of antiphospholipid syndrome (APS), vascular thrombosis should be accompanied with the presence of aPLs. The aim of this study was to investigate the presence of aPLs in severe COVID-19 female patients and to establish their association with the actual vascular thrombosis, thrombosis in personal history and pregnancy complications.

Methods: In 35 female patients hospitalized with severe COVID-19 pneumonia from March to May 2022, vascular thrombosis and pregnancy complications were recorded during the entire hospital stay and in their medical history. Females were also tested for nine types of aPLs at 4 time points (admission, exacerbation and discharge from hospital and at 3-month follow-up): anticardiolipin (aCL), anti-β2-glycoproteinI (anti-β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM/IgG/IgA isotypes. Because we used anticoagulants at therapeutic doses, we could not use the LA test, even with neutralizers, as these are only effective at low and typically preventive LMWH doses (0.8–1.0 U/mL); instead, the aPS/PT test was performed. Positive values were defined as those above the 99th percentile of the healthy control population. Statistical analysis was performed using SPSS 21 (NY, USA IBM Corp. Released 2021, IBM SPSS Statistics for Windows).

Results: During hospitalization, aPLs were tested positive at least once in 51.4% of females. All 5.7% of patients that passed away were tested aPLs negative at admission and worsening (one had pulmonary artery thrombosis and one microthrombosis). Personal anamnesis (PA) for thromboembolism was verified for 4 patients, at admission all of them tested aPLs negative, however transition to aPLs positivity at discharge (as the disease subsided) was detected in 75%  (all with deep vein thrombosis in PA) due to newly- positive aCL IgG at discharge seen in 75% added with positive aCL IgM in 50%. At follow-up,  one female remained positive for aCL IgG, one negativized and one one did not appear.  None of the women in our cohort were pregnant, and none of them became pregnant while at the hospital and in the follow-up. In their personal history, two women had abortions after 10^th week of gestation, but none of them tested positive for aPLs at admission or follow-up.

Conclusion: The incidence of APS in our cohort was 2.8%, whereas in general population it ranges from 0.001% to 0.002%. This high incidence was mostly due to deep vein thrombosis in womens personal history. Therefore, it is advised that all females with personal anamnesis of deep vein thrombosis in the past who had suffered severe COVID-19 and who plan to conceive should be tested for aPLs once and in positive cases retested 3 months later, in order to rule out the APS diagnosis and order appropriate therapy during pregnancy. Also, suppression of the ovaries related to COVID-19 in the post-COVID syndrome could be the reason for infertility [4].

Abstract

The data about pregnancy while having  low ejection fraction are scare, since pregnancy is not recommended for women with ejection fraction less than 30%. There is an increased risk for obstetrical complications and adverse maternal-fetal outcomes. Pregnancy is a rough Journey for this group of patients. However, successful pregnancy can be achieved when cardiac complications are managed during pregnancy.  The early recognitions of women at risk of cardiovascular event and early referral can optimize maternal and neonatal outcomes with close collaboration between the maternal-fetal medicine specialist and the cardiologist.⁵ The study aim was to a to assess the experience of our tertiary center with regards to adverse maternal outcome for women with Ejection fraction ≤30 % compared to those with EF > 30% in our tertiary center. The fetal and obstetrics outcome for pregnancies with EF ≤30% was compared to that for pregnancies with an EF> 30%.

Methodology: After receiving approval of the local Ethical Board Review a retrospective study was conducted at King Faisal Specialist Hospital and Research Center (KFSHRC) city of Riyadh, Kingdom of Saudi Arabia. Our study population included women with cardiomyopathy ( acquired or congenital heart) who were followed up or delivered in KFSH&RC from period of January 2004 till March 2020. Cases were identified by reviewing database from Cardiac Center Echocardiograph and maternal fetal medicine unit. The data on maternal and fetal outcome were gathered from the hospital medical records. An adverse maternal outcome included: death, hospitalization due to decompensated heart failure, worsening cardiovascular status during pregnancy. Adverse fetal outcomes included: miscarriages, termination of pregnancy, FGR, placental insufficiency. Obstetrics complications included: complications related to mode of deliver, Antepartum hemorrhage, postpartum hemorrhage or preeclampsia.

Results: Our study included 44 subjects, examining the differences between those with an ejection fraction greater than 30 (n = 21 subjects) and those with an ejection fraction less than or equal to 30 (n = 23) with respect to demographics, co-morbidities, and outcomes (maternal, pregnancy, fetal, ultrasound, and baby).  There was no evidence of any differences in the demographics.  From among the co-morbidites, there was a statistically higher rate of dilated cardiomyopathy and lower rate of rheumatic heart disease in those with a lower ejection fraction.  Also, women with a lower ejection fraction tended to deliver through a means other than simple vaginal delivery.  There was a significant association (p = 0.0296) indicating that individuals with a lower ejection fraction tended to have a lower gestational age at delivery. The information on whether the pregnancy resulted in a live birth was available for all but one of the mothers.  Across all the mothers, 32 (74%) resulted in a live birth and 11 did not.  The percentage of pregnancies resulting in a live birth in the group for which the ejection fraction was greater than 30 was 90% and that in the group for which the ejection fraction was less than or equal to 30 was 59% (p = 0.0339).  From among the ultrasound and baby outcomes, only the rate of the baby being discharged alive differed statistically between the two ejection fraction groups, with those mothers having a lower ejection fraction experiencing fewer babies being discharged alive (p = 0.0310).

CONCLUSION: In conclusion, Women with low ejection fraction are at increased risk of maternal-fetal complications. In our study, the lower the EF ( ≤30) the worse was the fetal and neonatal outcomes, however in terms of the maternal outcomes; it was the same wither the EF was low vs ultra-low. Yet These group of patient need to be counselled about the facts of poor obstetrical outcomes with emphasis on preconceptual counselling.

Abstract

Since the mid-1950s, over a million children have departed their low resource birth countries to join families in countries throughout Europe, Canada, Australia, the United States and elsewhere. This has always raised questions about poverty and privilege. Now the practice is near extinct and there has been a rise in commercial global surrogacy. This presentation will review the history of intercountry adoption, including contemporary data, while considering human rights and specifically the Convention on the Rights of the Child. Then, a turn to commercial surrogacy dynamics, from a global perspective, will feature original research evidence from India. This interview research, which was ultimately a study of poverty, found that surrogate mothers did not report exploitation in the context of extreme poverty and limited opportunities for women. Again, human rights will be considered, specifically the Convention on the Elimination of Discrimination Against Women. In sum, the presentation will end with questions about regulation in this global fertility frontier with so many vulnerabilities of women in low resource countries. Also considered will be the United States as it is the number one source of children born via surrogacy.