Early Identification of the Maternal, Placental, and Fetal Dialog in Gestational Diabetes and Its Prevention

Gestational diabetes mellitus (GDM) complicates between 5 and 12% of pregnancies, with associated maternal, fetal, and neonatal complications. The ideal screening and diagnostic criteria to diagnose and treat GDM have not been established and, currently, diagnostic use with an oral glucose tolerance test occurs late in pregnancy and produces poor reproducibility. Therefore, in recent years, significant research has been undertaken to identify a first-trimester biomarker that can predict GDM later in pregnancy, enable early intervention, and reduce GDM-related adverse pregnancy outcomes. Possible biomarkers include glycemic markers (fasting glucose and hemoglobin A1c), adipocyte-derived markers (adiponectin and leptin), pregnancy-related markers (pregnancy-associated plasma protein-A and the placental growth factor), inflammatory markers (C-reactive protein and tumor necrosis factor-α), insulin resistance markers (sex hormone-binding globulin), and others. This review summarizes current data on first-trimester biomarkers, the advantages, and the limitations. Large multi-ethnic clinical trials and cost-effectiveness analyses are needed not only to build effective prediction models but also to validate their clinical use.

Outcomes of Neonates Exposed to Buprenorphine versus Methadone in Utero: A Systematic Review and Meta-Analysis of Safety in the Fetus and Neonate

We assessed the prevalence of neonatal abstinence syndrome (NAS) and fetal growth outcomes in neonates exposed to methadone compared to buprenorphine in utero. Three authors assessed the titles and abstracts of all potentially eligible studies. The selection criteria were randomized controlled trials and observational cohort studies from January 2000 to January 2020 which indexed and reported original data for occurrence of NAS and fetal growth outcomes in pregnant people who received methadone vs. buprenorphine treatment. The quality and possible bias of each study was assessed using the Cochrane-risk-of-bias tool. Data were pooled to compare the occurrence of NAS and fetal growth restriction among women who received methadone vs. buprenorphine treatment. Of the 106 articles screened, 1 randomized controlled trial and 5 observational cohort studies including 2041 pregnancies fulfilled the inclusion criteria. Buprenorphine is associated with less NAS and improved growth outcomes compared to methadone. (OR = 0.515; p-value < 0.001). Compared to methadone, buprenorphine is associated with less adverse neonatal outcomes in terms of gestational age at birth, birthweight, and head circumference. With the prevalence of NAS continuing to rise, this study adds to the expanding academic research aimed at creating safer treatment protocols.

A History of Neonatal Uterine Bleeding and Its Significance

Bleeding in newborns and young girls fascinated writers for more than a millennium. Initially, there was confusion between neonatal bleeding, early menstruation due to precocious puberty, and hemorrhage due to disease. During the 19th century descriptions appeared of what is referred to today as ‘neonatal menstruation’ or ‘neonatal uterine bleeding’. By the turn of the century, Halban linked bleeding to active substances present during pregnancy and hypothesized that, while the maternal uterus reacts with decidua formation, the “weaker” fetal uterus reacts only with menstrual-like changes. Despite this clear description, several alternative theories endured for decades. Bleeding was believed to be due to a ‘catarrhal’ or neoplastic state of the genital tract, pulmonary circulatory disorder, congenital heart malformations, closure of the umbilical cord or affections of the intestine. During the 1950s, progesterone response and resistance were proposed to explain the pathogenesis of bleeding and its low incidence. The fetal endometrium is resistant to the high circulating progesterone. A decidual response is infrequent and results in menstrual shedding upon progesterone withdrawal after birth. Further research linked fetal stress consequent to pregnancy complications and post-maturity to increased incidence and preterm birth to reduced incidence of neonatal uterine bleeding.

Prenatal Diagnosis of Severe Fetal Hydronephrosis Due to Pyeloureteral Junction Syndrome with False Neonatal Resolution

A case of severe fetal hydronephrosis due to isolated bilateral stenosis of the pyelo-ureteral junction was diagnosed at our centre. Surprisingly, a negative renal ultrasound scan was performed on the 3rd postnatal day. An ultrasound follow-up showed severe bilateral pyelectasis a few weeks later. The infant underwent bilateral pyeloplasty at six months of age with an excellent outcome. Such a neonatal picture may be due to the reduction of urinary output secondary to excessive postnatal weight loss and dehydration. In this case, prenatal ultrasound result was more reliable than postnatal ultrasound, emphasizing the importance of postnatal urologic follow-up after prenatal indication.

A 10-Year Perspective on the Utility of Three Adjuvants Often Used in IVF: Growth Hormone, Melatonin and DHEA

Since 2010, numerous studies reported from PIVET, a pioneer IVF facility established over 40 years ago, have explored the use of three adjuvants designed to improve laboratory and clinical outcomes in cases where a poor prognosis has been demonstrated. The adjuvants reported commenced with recombinant growth hormone (rGH), followed by dehydroepiandrosterone (DHEA) after developing a unique troche to avoid the first-pass effect and, subsequently, melatonin. The studies show that rGH is beneficial in the situation where women have poor-quality embryos in the setting of additional poor prognosis factors, such as advanced female age, a very low ovarian reserve, an insulin growth factor profile in the lowest quartile or recurrent implantation failure. The studies also imply that the adjuvants may actually reduce live birth productivity rates if used on women without poor prognosis factors; hence, further studies, which can now be better designed, should be undertaken to explore the notion of underlying adult growth hormone deficiency in some cases as well as the suggestion that DHEA can provide equivalent benefits in some poor prognosis settings. Melatonin showed no suggestive benefits in any of the studies and can be excluded from consideration in this context. Future studies should compare rGH and DHEA with a focus on those women who have poor embryo quality with additional poor prognosis factors. Such trials should be extended to 12 weeks to cover the entire period of oocyte activation.

Risk Factors for Early and Late Onset Preeclampsia in Reunion Island: Multivariate Analysis of Singleton and Twin Pregnancies. A 20-Year Population-Based Cohort of 2120 Preeclampsia Cases

Objectives: To develop a multivariate model for risk factors specific to early onset preeclampsia (EOP) and late onset preeclampsia (LOP) in our entire population (singleton and twin pregnancies). Material and methods: 20 year-observational population-based historical cohort study (2001–2020). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion’s maternity ward. A standardized validated epidemiological perinatal database was used. Results: During the 20-year period, there were 81,834 pregnancies and 83,497 infants born, 1232 dichorionic and 350 monochorionic twin pregnancies. There were 2120 cases of preeclampsia, of which 2001 were preeclamptic singleton pregnancies and 119 twin pregnancies (incidence 7.5% in twin pregnancies vs. 2.5% singletons, OR 3.0, p < 0.001). Independent risk factors for EOP and LOP in a multivariate model (controlling for the two major confounders: maternal ages—both risks for EOP and LOP, and maternal pre-pregnancy BMI—specific risk factor for LOP) were: history of preeclampsia (adjusted OR (aOR) 11.7 for EOP, 7.8 for LOP, p < 0.0001), chronic hypertension (aOR 7.3 for EOP, 3.9 for LOP, p < 0.0001), history of perinatal death (aOR 2.2 for EOP, p < 0.0001 and 1.48 for LOP, p = 0.007), primipaternity (aOR 3.0 for EOP and 3.6 for LOP, p = 0.001), dizygotic twin pregnancies (aOR 3.7 for EOP, p < 0.0001 and 2.1 for LOP, p = 0.003), monozygotic twin pregnancies (aOR 3.98 for EOP, p = 0.003 and non-significant (NS) for LOP), ovulation induction (aOR 5.6 for EOP, p = 0.004 and NS for LOP), and in vitro fertilization (aOR 2.8 for EOP, p = 0.05 and NS for LOP). Specific to LOP and NS for EOP: renal diseases (aOR for LOP 2.9, p = 0.007) and gestational diabetes mellitus (aOR 1.2, p = 0.04). Conclusions: Maternal ages over 35 years, chronic hypertension, history of preeclampsia, ovulation induction, in vitro fertilizations, history of perinatal deaths and twin pregnancy (in our experience, especially mono zygotic twin pregnancies) are significant risk factors for EOP. New paternity is an independent factor for both EOP and LOP.

Effect of Microfluidic Sperm Separation vs. Standard Sperm Washing Processes on Laboratory Outcomes and Clinical Pregnancy Rates in an Unselected Patient Population

A prospective, multicenter, randomized, sibling oocyte study was conducted with 86 couples to evaluate if a microfluidic sperm separation device improved ICSI sperm selection and subsequent cycle outcomes of fertilization, blastocyst utilization, ploidy, and clinical pregnancy rate when applied to a general patient population. Patients with at least 10 metaphase II oocytes were enrolled in the study and sibling oocyte groups were split in half. One half of the oocytes underwent ICSI with the control processed sperm and the other half were injected with sperm sorted by the ZyMōt microfluidic sperm separation device. Fertilization rate was recorded and resulting blastocysts were biopsied and evaluated for ploidy status with NGS. Euploid, non-mosaic embryos were randomly selected for single embryo transfer. A total of 787 oocytes were evaluated in the ZyMōt group and 777 in the control group. No statistical differences were observed between ZyMōt and control processing methods in any of the study outcomes evaluated. It is possible that the selection of normal, progressive sperm for ICSI, and the repair capacity of oocytes are sufficient to promote normal embryonic development in the general infertility population.

Pushing the Limits of Prenatal Ultrasound: A Case of Dorsal Dermal Sinus Associated with an Overt Arnold-Chiari Malformation and a 3q Duplication

We present a case of a fetus with cranial abnormalities typical of open spina bifida but with an intact spine shown on both ultrasound and fetal MRI. Expert ultrasound examination revealed a very small tract between the spine and the skin, and a postmortem examination confirmed the diagnosis of a dorsal dermal sinus. Genetic analysis found a mosaic 3q23q27 duplication in the form of a marker chromosome. This case emphasizes that meticulous prenatal ultrasound examination has the potential to diagnose even closed subtypes of neural tube defects. Furthermore, with cerebral anomalies suggesting a spina bifida, other imaging techniques together with genetic tests and measurement of alpha-fetoprotein in the amniotic fluid should be performed.

Human Milk and Brain Development in Infants

Human milk is considered the most advantageous source of nourishment for infants. Even though there is no ideal composition of human milk, it still contains a unique combination of components that contribute to brain development. The aim of this review is to provide an overview on the possible correlation of human milk with the neurodevelopment of infants, with a special emphasis on myelination and epigenetic modifications. Research in human milk is a rapidly expanding field and cutting-edge technologies might contribute to identify specific mechanisms underlying the beneficial effects on human milk on neurodevelopment.

SARS-CoV-2, Endothelial Dysfunction, and the Renin-Angiotensin System (RAS): A Potentially Dangerous Triad for the Development of Pre-Eclampsia

SARS-CoV-2 represents the greatest epidemiological, clinical, and social challenge the human being has had to face in this century. SARS-CoV-2 is not merely a respiratory virus, as its target cells range from upper airway respiratory cells to pulmonary cells but also and above all to the cardiovascular cells, such as pericytes and endothelial cells. Indeed, the pathology related to SARS-CoV-2, COVID-19, may be defined as a thromboinflammatory syndrome in its most severe form, characterized by sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulopathy (DIC), which is prevalent in individuals already presenting a chronic level of inflammation (e.g., obese individuals, elderly) and hypertension. Pregnancy is not only an inflammatory-prone condition but is characterized by a consistent rearrangement of the blood circulation and coagulation profile. Cardiac output increases while arterial systolic and diastolic pressure decrease, regardless of the activation of the RAS system. ACE2, the SARS-CoV-2 entry receptor into the host cells, which transforms Ang II in Ang 1–7, is highly expressed in endothelial, smooth muscle cells and pericytes of placental villi, regulating blood pressure and fetal development. Pre-eclampsia is a pregnancy disorder characterized by hypertension and low levels of ACE2, endothelial dysfunction, and a high production of pro-inflammatory cytokines, resembling COVID-19 manifestations. Whereas pre-eclampsia and COVID-19 have overlapping clinical features, a role for SARS-CoV-2 as a leading cause of pre-eclampsia in COVID-19 positive pregnant women has not been clarified yet. In this mini-review, we will explore the possibility of the existence of such a link, focusing on the role of endothelial dysfunction and RAS in both pre-eclampsia and SARS-CoV-2-induced COVID-19 pathogenesis.