Is Glycated Hemoglobin A1c Level Associated with Adverse Pregnancy Outcomes of Women Affected by Pre-Gestational Diabetes?

Background and Objectives: This observational study aims to determine the correlation between glycemic control with the HbA1c value and adverse obstetric outcome in women affected by pre-gestational diabetes. Materials and Methods: A retrospective analysis has been performed at the University Hospital of Udine. Only patients with a singleton pregnancy, pre-gestational diabetes, and known level of Hb A1c throughout pregnancy were included in the study. Results: According to the HbA1c level, at the beginning of pregnancy, 49 patients with HbA1c ≤ 7.0% were compared with 45 patients with HbA1c > 7.0%. Maternal age at diagnosis of the disease was significantly higher in the group with HbA1c ≤ 7% than in the group with HbA1c > 7%, 26.00 (18.00-32.00) vs. 20.00 (12.50-27.00). Women with HbA1c ≤ 7.0% reached, at term of pregnancy, significantly lower levels of HbA1c, 5.8% (5.7-6.0) vs. 6.7% (6.3-7.3). Daily insulin units were statistically different between the two groups at the end of pregnancy (47.92 (39.00-67.30) vs. 64.00 (48.00-82.00)). Proteinuria was significantly higher in the group with HbA1c > 7.0%, who delivered at earlier gestational age (37.57 (35.57-38.00) vs. 38.14 (38.00-38.43). Moreover, women with HbA1c > 7.0% had a significantly higher prevalence of an adverse composite outcome. Of note, in multivariate logistic regression analysis, pregnancy complications were significantly correlated to pre-pregnancy HbA1c > 7.0% (OR 2.95 CI.95 1.16-7.48, p < 0.05) independently of age, insulin treatment, and type of diabetes. Conclusions: Our data, obtained from a single-center cohort study, suggest that starting pregnancy with poor glycemic control might predict more complex management of diabetes in the following trimesters.

Maternal age and the risk of adverse pregnancy outcomes: a retrospective cohort study.

BACKGROUND: The increased potential for negative pregnancy outcomes in both extremes of reproductive age is a well-debated argument. The aim of this study was to analyze the prevalence and the outcome of pregnancies conceived at extreme maternal ages. METHODS: This retrospective study considered all single consecutive pregnancies delivered in a tertiary referral center between 2001 and 2014. Patients were categorized into 4 groups according to maternal age at delivery (< 17 years; 18-28 years; 29-39 years; > 40 years). The following outcomes were considered (amongst others): pregnancy-related hypertensive disorders (PRHDs), neonatal resuscitation (NR), neonatal intensive care unit (NICU) admission, periventricular leucomalacia (PVL), and grade 3 and 4 intraventicular hemorrhage (IVH). RESULTS: During the considered period 22,933 single pregnancies gave birth in our unit. We observed 71 women aged < 17 years, and 1552 aged > 40 years. In each year throughout the study period, there was a significant increment in maternal age of 0.041 years (95% CI 0.024-0.058) every new year. Multivariate analysis concluded out that maternal age over 40 years was an independent risk factor for preterm delivery (OR 1.36 95% CI 1.16-1.61, p < 0.05, PRHDs (OR 2.36 95% CI 1.86-3.00, p < 0.05), GDM (OR 1.71 95% CI 1.37-2.12, p < 0.05) cesarean section (OR 1.99 95% CI 1.78-2.23, p < 0.05), abnormal fetal presentation (OR 1.29 95% CI 1.03-1.61, p < 0.05), and fetal PVL (OR 3.32 95% CI 1.17-9.44, p < 0.05). We also observed that maternal age under 17 years or over 40 years was an independent risk factor for grade 3 or 4 neonatal IVH (OR 2.97 95% CI 1.24-7.14, p < 0.05). CONCLUSIONS: These findings confirm a negative impact of extreme maternal ages on pregnancy. These results should be carefully taken into account by maternal care providers in order to inform women adequately, supporting them in understanding potential risks associated with their procreation choices, and to improve clinical surveillance.

A 16q deletion involving FOXF1 enhancer is associated to pulmonary capillary hemangiomatosis.

BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is an uncommon pulmonary disorder, with variable clinical features depending on which lung structure is affected, and it is usually linked to pulmonary arterial hypertension. Congenital PCH has been very rarely described and, so far, the only causative gene identified is EIF2AK4, which encodes for a translation initiation factor. However, not all PCH cases might carry a mutation in this gene. CASE PRESENTATION: We report the clinical and cytogenetic characterization of a patient (male, newborn, first child of healthy non-consanguineous parents) died after three days of life with severe neonatal pulmonary hypertension, due to diffuse capillary hemangiomatosis diagnosed post mortem. Conventional karyotyping, Microarray-Based Comparative Genomic Hydridization (CGHa) and quantitative PCR were performed. CGHa revealed a heterozygous chromosome 16q23.3q24.1 interstitial deletion, spanning about 2.6 Mb and involving a FOXF1 gene enhancer. Quantitative PCR showed that the proband's deletion was de novo. Microsatellite analysis demonstrate that the deletion occurred in the maternal chromosome 16. CONCLUSION: FOXF1 loss of function mutation have been so far identified in alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), a lung disease different from PCH. Our data suggest the hypothesis that disruption of the FOXF1 gene enhancer could be a genetic determinant of PCH. Moreover, our findings support the idea that FOXF1 is a paternally imprinted gene.

A two-year retrospective study of the neonatal emergency transport service in Northeast Italy.

BACKGROUND: Some newborns require acute transport to a Neonatal Intensive Care Unit (NICU) due to unpredicted or unpredictable reasons. OBJECTIVE: To describe the activity of the Neonatal Emergency Transport Service (NETS) in Northeast Italy. METHODS: An observational retrospective study was performed between 1 January 2018, and 31 December , 2019. RESULTS: A total of 133 transports were collected, with a neonatal transport index of 1.4%. Infants ≤2500 grams were more frequently transferred by NETS than those in the normal group (n = 34/563, 6.0% vs. n = 99/8,437, 1.2%; p < .001). The incidence of preterm birth among transferred newborns was 42/133 (31.6%). For the newborns with >2500 grams, there was a low incidence of a cesarean birth compared to vaginal delivery (23.2% versus 63.5%; p = .001), while the percentages were reversed in the group of infants ≤2500 grams (67.7% versus 20.6%) (p = .001). Infant stabilization time was higher in the underweight group compared to those weighed >2500 grams (31.5 versus 23.0 min; p < .001), as well as the median length of stay in NICU (18.0 versus 8.0 days, respectively, p < .001). The group of infants ≤2500 grams received more intravenous therapy (47.1% vs. 26.2%) and invasive ventilation (26.5% vs. 8.1%), compared to the group of infants who weighed >2500 grams. CONCLUSIONS: This study described a local reality by showing the characteristics of the neonatal transports that took place in a metropolitan area in Northeast Italy. Wider database is necessary to achieve a better knowledge in the field of perinatal outcomes.

Partial vs. complete course of antenatal corticosteroid prophylaxis: An Italian single center retrospective study.

Introduction: This study aimed to compare the outcomes of preterm infants given 12 vs. 24mg of betamethasone prophylaxis to understand whether a partial course of antenatal corticosteroids (CCS) could prevent or mitigate the major preterm birth complications. Methods: This is a retrospective single-center cohort study including neonates born between 24 and 34 weeks of gestation from 2001 to 2019 at the University Hospital of Udine. The study population was divided into two groups: one group received 12mg, and another received a 24mg dose of betamethasone before the delivery. A separate analysis was performed for single and multiple pregnancies. The two groups were evaluated for various neonatal outcomes. Results: The study population included a total of 1,258 pregnancies and 1,543 neonates delivered between 24 and 34 weeks of gestation, of which 1,022 (803 single and 219 multiple pregnancies) were exposed to the complete CCS prophylaxis, whereas 236 (192 single and 44 multiple pregnancies) received the incomplete CCS prophylaxis. In single pregnancies, as for maternal characteristics, the most significant differences observed between the two groups are the following: a higher prevalence of spontaneous vaginal deliveries in the incomplete CCS prophylaxis (36.46 vs. 23.91%) and, by contrast, a higher prevalence of cesarean deliveries in the complete CCS prophylaxis group (75.72 vs. 63.02%). As for neonatal outcomes, the low Apgar score in the first and fifth min was significantly more prevalent in the incomplete CCS prophylaxis group compared with the complete CCS prophylaxis group. The group of incomplete CCS prophylaxis reported a higher occurrence of the following outcomes: IVH grade 3-4 (7.81 vs. 3.74%, p < 0.05), PVL (7.29 vs. 1.99% p < 0.05), ROP (23.96 vs. 18.06% p = 0.062), and RDS (84.38 vs. 78.83% p = 0.085). After adjusting for covariates, the complete CCS prophylaxis group in single pregnancies was significantly protective for IVH grade 3-4, PVL, and low Apgar's scores. Similar results were found in multiple pregnancies except for RDS. Discussion: This retrospective single-center cohort study found that, compared with preterm infants treated with 24mg betamethasone in utero, those given half course of betamethasone had a significantly higher prevalence of IVH grade 3-4, PVL, RDS, and lower Apgar scores at 1 and 5 min. In conclusion, the evidence from this single-center retrospective study supports the preference for the complete CCS prophylaxis in women at risk of preterm birth because of its beneficial effect on the main adverse outcomes.

In vitro fertilization is associated with placental accelerated villous maturation.

OBJECTIVE: Accelerated placental maturation is regarded as a sign of vascular malperfusion and is often interpreted as a compensatory response by the placenta. In vitro embryo culture affects placental development. This study assessed placental maturation in spontaneous conceived and in vitro conceived pregnancies. METHODS: Retrospective cohort study on a single center between 2014 and 2017. For this study, preterm placentas of singleton pregnancies between 24 and 36 weeks were considered. Routine placental examinations were retrospectively reviewed. RESULTS: During the considered period, 423 placentas of singleton pregnancies were assessed. Three hundred ninety-six placentas were from spontaneous conception and 20 from in vitro fertilization and embryo transfer (IVF/ET). IVF/ET was significantly associated with accelerated villous maturation (AVM) and distal villous hypoplasia (DVH) (P<0.05). CONCLUSIONS: Placental AVM and DVH were significantly associated with in vitro fertilization in singleton pregnancies. This result supports the hypothesis that AVM is a compensatory response by the placenta to improve its transport capacity in specific settings such as in vitro fertilization.

A novel de novo HDAC8 missense mutation causing Cornelia de Lange syndrome.

BACKGROUND: Cornelia de Lange syndrome (CdLS) is a rare and clinically variable syndrome characterized by growth impairment, multi-organ anomalies, and a typical set of facial dysmorphisms. Here we describe a 2-year-old female child harboring a novel de novo missense variant in HDAC8, whose phenotypical score, according to the recent consensus on CdLS clinical diagnostic criteria, allowed the diagnosis of a non-classic CdLS. METHODS: Clinical exome sequencing was performed on the trio, identifying a de novo heterozygous variant in HDAC8 (NM_018486; c. 356C>G p.Thr119Arg). Molecular modeling was performed to evaluate putative functional consequence of the HDAC8 protein. RESULTS: The variant HDAC8 c.356C>G is classified as pathogenic following the ACMG (American College of Medical Genetics and Genomics)/AMP (Association for Molecular Pathology) guidelines. By molecular modeling, we confirmed the deleterious effect of this variant, since the amino acid change compromises the conformational flexibility of the HDAC8 loop required for optimal catalytic function. CONCLUSION: We described a novel Thr119Arg mutation in HDAC8 in a patient displaying the major phenotypic traits of the CdLS. Our results suggest that a modest change outside an active site is capable of triggering global structural changes that propagate through the protein scaffold to the catalytic site, creating de facto haploinsufficiency.

Placental acute inflammation infiltrates and pregnancy outcomes: a retrospective cohort study.

Chorioamnionitis can be either an infection or a sterile inflammation. This study aims to analyze the prevalence of acute inflammatory lesions of the placenta, the association with a positive result of the microbiological examination, and the fetal-maternal outcomes. This retrospective study considered all single, consecutive pregnancies and their placental pathological examination during 2014-2017. The evidence of funisitis, chorionic vasculitis, and chorioamnionitis was assessed by a pathologist, including stage and grade. Moreover, maternal fever, placental microbiological examination, and neonatal outcomes were also recorded. Among the 5910 pregnancies in the considered period, 1770 had a placental pathological examination, and 358 (6.06%) had acute placental inflammation. Microbiological examination was performed in 125 cases, revealing 64 cases with a positive microbiological outcome. In the presence of acute placental inflammation, there was a higher rate of neonatal cardiopulmonary resuscitation, admission to neonatal intensive care unit, and postnatal death of the newborn. Multivariate analysis inferred that acute inflammation of membranes was a risk factor for neonatal cardiopulmonary resuscitation (OR 2.12; CI.95 1.36-3.31; p < 0.05), acute funisitis was a risk factor for admission to intensive neonatal care unit (OR 3.2; CI.95 1.67-6.12; p < 0.05), and chorionic vasculitis was a risk factor for postnatal death of the newborn (OR 5.38; CI.95 1.37-21.06; p < 0.05). The prevalence of chorioamnionitis was 6.06%, and about half of the cases were sterile inflammation. Chorioamnionitis was associated with higher rates of adverse fetal and neonatal outcomes; in particular, chorionic vasculitis was a risk factor for postnatal death.

The influence of timing of elective cesarean section on risk of neonatal pneumothorax.

OBJECTIVE: To determine whether the timing of elective cesarean delivery at term influences the risk of neonatal pneumothorax. STUDY DESIGN: Chart reviews confirmed gestational age, delivery modalities, and diagnosis of pneumothorax of 66,961 term infants delivered in the Veneto region of northern Italy. Of these neonates, 17,783 (26.5%) were delivered by cesarean section, including 9988 elective (56.1%) and 7795 emergency (43.8%). RESULTS: In 5498 (55.0%) of neonates, an elective cesarean section was performed before 39 completed weeks. Fifty-nine neonates had pneumothorax diagnosed (0.88/1000 births). Neonates delivered by elective cesarean section had an increased incidence of pneumothorax (2.90/1000 births), in comparison with neonates delivered by emergency cesarean (1.53/1000 births; OR 4.21; 95% CI 2.02-8.74) or vaginally delivered (0.39/1000 births; OR 7.95; 95% CI 4.41-14.32). In elective cesarean sections there was a significant progressive reduction in the incidence of pneumothorax from week 37 0/7 to 37 6/7 onward (P < .01). CONCLUSIONS: The timing of elective cesarean section influences the pneumothorax risk. A reduction in neonatal iatrogenic pneumothorax would result if elective deliveries were performed after the 39 completed weeks of pregnancy.

70% Alcohol Versus Dry Cord Care in the Umbilical Cord Care: A Case-Control Study in Italy.

Recently the use of antibacterial agents to clean and dry the stump of the newborns' umbilical cord (UC) after birth has been abandoned by many neonatal units in favor of dry cord care. Aim of this study was to compare the occurrence of adverse events (AEs) and time to cord separation among newborns treated with dry cord care versus 70% alcohol in an Italian Academic Hospital (AH).From December 2014 to March 2015, 239 infants were born at the AH. The number of eligible infants was 200 and they were equally assigned to either case group (dry cord care) or control group (70% alcohol, standard procedure). Standard cord care consisted in 1 application of 70% alcohol at birth followed by other 2 times a day, while experimental dry cord care procedure was executed by the only application of a sterile gauze around the base of the UC at the 1st day of life and after the cord has been exposed to air off the diaper edge. The time to UC separation and any AEs such as local and systemic infections, hemorrhage, and granuloma formation were reported by mothers.We found a significant difference in the mean cord separation time between the 2 groups (dry cord care: 10.1 days [standard deviation, SD = 4.0] vs 70% alcohol: 12.0 days [SD = 4.2]; P < 0.001), while no significant AEs resulted. Incidence rate of granuloma was 0.67 × 1000 days of life in dry cord care group.Dry cord care is an easy, straight-forward, and safe method of handling the UC in healthy newborn infants born in a high-income hospital setting.