Current knowledge of prenatal diagnosis of mosaic autosomal trisomy in amniocytes: karyotype/phenotype correlations.

Genetic counseling for prenatal diagnosis of autosomal trisomy is complex because of the uncertainty of outcome, which is important for management decisions. Compilation of cases of prenatally diagnosed autosomal trisomies in amniocytes has been done previously in an attempt to elucidate the clinical phenotype of these pregnancies. It has been greater than a decade since these studies were completed. To update this work, we reviewed cases reported in the literature since that time. These cases are correlated with the prior reports to increase knowledge about outcomes and to hopefully improve the data available for genetic counseling. The risk of abnormal outcome can be summarized as: very high risk (>60%) for 47,+2/46; 47,+9/46; 47,+16/46; 47,+20/46; and 47,+22/46; high risk (40-59%) for 47,+5/46; 47,+14/46; and 47,+15/46; moderately high risk (20-39%) for 47,+7/46 47,+12/46; and 47,+17/46; moderate risk (up to 19%) for 47,+6/46 and 47,+8/46, and none were low risk. 47,+6/46 was originally indeterminate, 47,+7/46 was originally moderate risk, 47,+9/46 was originally high risk, and 47,+17/46 was originally low risk.

Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: prospective cohort study.

OBJECTIVE: To investigate maternal immunoglobulins' (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants. DESIGN: A prospective observational study. SETTING: Public healthcare system in Santa Clara County (California, USA). PARTICIPANTS: Women with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021. OUTCOMES: SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life. RESULTS: Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p<0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared with <60 days (1.2 vs 0.6, p<0.0001). Infant IgG seroreversion rates over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4 of 48), 12% (3 of 25), and 38% (5 of 13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to 6 months of age. Two newborns showed seroconversion at 2 weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. CONCLUSIONS: Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than 2 months before delivery. Maternally derived passive immunity may persist in infants up to 6 months of life. Neonates are capable of mounting a strong antibody response to perinatal SARS-CoV-2 infection.

Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: Prospective cohort study.

OBJECTIVE: To investigate maternal immunoglobulins' (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterize neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively- and passively-acquired SARS-CoV-2 antibodies in infants. DESIGN: A prospective observational study. SETTING: A public healthcare system in Santa Clara County (CA, USA). PARTICIPANTS: Women with SARS-CoV-2 infection during pregnancy and their infants were enrolled between April 15, 2020 and March 31, 2021. OUTCOMES: SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life. RESULTS: Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and eight with severe-critical symptoms. Of the 147 newborns, two infants showed seroconversion at two weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56-0.73) and the cord blood was 58% (95% CI 0.49-0.66). IgG levels significantly correlated between the maternal and cord blood (Rs= 0.93, p< 0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared to <60 days (1.2 vs. 0.6, p=<0.0001). Infant IgG negative conversion rate over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4/48), 12% (3/25), and 38% (5/13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to six months of age. CONCLUSIONS: Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than two months before delivery. Maternally-derived passive immunity may protect infants up to six months of life. Neonates mount a strong antibody response to perinatal SARS-CoV-2 infection.

Eliminating Risk of Intubation in Very Preterm Infants with Noninvasive Cardiorespiratory Support in the Delivery Room and Neonatal Intensive Care Unit.

INTRODUCTION: Avoiding intubation and promoting noninvasive modes of ventilator support including continuous positive airway pressure (CPAP) in preterm infants minimizes lung injury and optimizes neonatal outcomes. Discharge home on oxygen is an expensive morbidity in very preterm infants (VPI) with lung disease. In 2007 a standardized bundle was introduced for VPI admitted to the neonatal care unit (NICU) which included delayed cord clamping (DCC) at birth and noninvasive ventilation as first-line cardiorespiratory support in the delivery room (DR), followed by bubble CPAP upon NICU admission. OBJECTIVE: Our goal was to evaluate the risk of (1) intubation and (2) discharge home on oxygen after adopting this standardized DR bundle in VPI born at a regional perinatal center and treated in the NICU over a ten-year period (2008-2017). MATERIALS AND METHODS: We compared maternal and neonatal demographics, respiratory care processes and outcomes, as well as neonatal mortality and morbidity in VPI (< 33 weeks gestation) and extremely low birth weight (ELBW, < 1000 g) subgroup for three consecutive epochs: 2008-2010, 2011-2013, and 2014-2017. RESULTS: Of 640 consecutive inborn VPI, 55% were < 1500 g at birth and 23% were ELBW. Constant through all three epochs, DCC occurred in 83% of VPI at birth. There was progressive increase in maternal magnesium during the three epochs and decrease in maternal antibiotics during the last epoch. Over the three epochs, VPI had less risk of DR intubation (23% versus 15% versus 5%), NICU intubation (39% versus 31% versus 18%), and invasive ventilation (37% versus 30% versus 17%), as did ELBW infants. Decrease in postnatal steroid use, antibiotic exposure, and increase in early colostrum exposure occurred over the three epochs both in VPI and in ELBW infants. There was a sustained decrease in surfactant use in the second and third epochs. There was no significant change in mortality or any morbidity in VPI; however, there was a significant decrease in pneumothorax (17% versus 0%) and increase in survival without major morbidity (15% versus 41%) in ELBW infants between 2008-2010 and 2014-2017. Benchmarked risk-adjusted rate for oxygen at discharge in a subgroup of inborn VPI (401-1500 g or 22-31 weeks of gestation) is 2.5% (2013-2017) in our NICU compared with > 8% in all California NICUs and > 10% in all California regional NICUs (2014-2016). CONCLUSION: Noninvasive strategies in DR and NICU minimize risk of intubation in VPI without adversely affecting other neonatal or respiratory outcomes. Risk-adjusted rates for discharge home on oxygen remained significantly lower for inborn VPI compared with rates at regional NICUs in California. Reducing intubation risk in ELBW infants may confer an advantage for survival without major morbidity. Prenatal magnesium may reduce intubation risk in ELBW infants.

New body composition reference charts for preterm infants.

BACKGROUND: The American Academy of Pediatrics (AAP) has recommended that nutritional management of the preterm infant should aim to achieve body composition that replicates the in utero fetus, but intrauterine body composition reference charts for preterm infants are lacking. OBJECTIVE: Our objective was to create body composition reference curves for preterm infants that approximate the body composition of the in utero fetus from 30 to 36 wk of gestation. DESIGN: A total of 223 ethnically diverse infants born at 30 + 0 to 36 + 6 wk of gestation were enrolled. Inclusion and exclusion criteria were specified so that the sample would represent healthy appropriately growing fetuses (e.g., singleton, birth weight appropriate for their gestational age, and medically stable). Cross-sectional reference values were generated for fat mass (FM), fat-free mass (FFM), and percentage body fat (PBF) by gestational age (GA), with the use of air-displacement plethysmography (ADP) and the lambda-mu-sigma method for percentile estimation. RESULTS: GA-specific percentile values and a percentile and z score calculator for FFM, FM, and PBF are presented. These values aligned closely with ADP centile values published for term infants from 36 to 38 wk of gestation. The medians were also similar to the mean values for the reference fetus derived from chemical analysis previously. CONCLUSIONS: To our knowledge, these are the first body composition reference charts for total FM and FFM at birth in preterm infants to assist in following AAP guidelines. Future work will test the clinical utility of body composition monitoring for improving nutritional management in this population. This trial was registered at clinicaltrials.gov as NCT02855814.

Neurological and developmental outcomes of prenatally cocaine-exposed offspring from 12 to 36 months.

Second generation studies of prenatal cocaine exposure failed to find gross deficits after controlling for confounders. Concern remained that exposure could cause subtle deficits. This prospective, cohort study evaluated effects of cocaine on development at 12, 18, 24, and 36 months. From 1991-1993, 361 mother-infant pairs were recruited from the Children's Hospital of New York, Presbyterian Medical Center's prenatal clinic or delivery room suite. Mothers were assigned to the cocaine group based on report of prenatal cocaine use or positive urine toxicology. Control mothers were enrolled from the same clinic and matched for age and socioeconomic status (SES). Women with serious medical problems were excluded from either group. Of the retained cohort, at 12 months, 147 infants were exposed and 89 were unexposed case controls. Both groups were raised in impoverished environments with few supports. Developmental evaluations were conducted blinded to group. Cross-sectional analysis revealed cocaine-related deficits in neurological exams and speech across all time periods, in spite of catch up in weight, length, and head circumference. Overall analysis of development was evaluated using Generalized Estimating Equations regression analysis. Bayley Mental [Badj = -6.5 (CI--9.4, -3.5, p < or = 0.001)] and Psychomotor [Badj = -3.9 (CI--7.4, -0.5, p = 0.02)] Developmental Indices showed deficits after controlling for confounders. Males were more vulnerable to cocaine exposure for height, motor development, and emotional regulation. Dose-response relationships existed for abnormal neurological exams (Ptrends < 0.08), Mental Development Index (MDI) (Ptrend < 0.001), and Psychomotor Development Index (PDI) (Ptrend < 0.001) deficits. Although nonexposed children performed poorly, cocaine-exposed children showed worse performance. Both groups showed declines at 18 months in mental and psychomotor development from which only nonexposed children rebounded. Overall, cocaine exposure adds an additional risk to disadvantaged children's development. Cocaine-exposed children are less resilient to effects of these multiple risks.