Adetola Louis-Jacques

The very low birth weight infant microbiome and childhood health

This review describes current understandings about the nature of the very low birth weight infant (VLBW) gut microbiome. VLBW infants often experience disruptive pregnancies and births, and prenatal factors can influence the maturity of the gut and immune system, and disturb microbial balance and succession. Many VLBWs experience rapid vaginal or Caesarean births. After birth these infants often have delays in enteral feeding, and many receive little or no mothers own milk. Furthermore the stressors of neonatal life in the hospital environment, common use of antibiotics, invasive procedures and maternal separation can contribute to dysbiosis. These infants experience gastrointestinal dysfunction, sepsis, transfusions, necrotizing enterocolitis, oxygen toxicity, and other pathophysiological conditions that affect the normal microbiota. The skin is susceptible to dysbiosis, due to its fragility and contact with NICU organisms. Dysbiosis in early life may resolve but little is known about the timing of the development of the signature gut microbiome in VLBWs. Dysbiosis has been associated with a number of physical and behavioral problems, including autism spectrum disorders, allergy and asthma, gastrointestinal disease, obesity, depression, and anxiety. Dysbiosis may be prevented or ameliorated in part by prenatal care, breast milk feeding, skin to skin contact, use of antibiotics only when necessary, and vigilance during infancy and early childhood.

A positive association between umbilical cord RBC folate and fetal TL at birth supports a potential for fetal reprogramming

Telomere length (TL) has been studied extensively in adults; however, limited information exists regarding maternal influences on TL in utero. The objective of this study was to investigate the relationship between fetal red blood cell (RBC) folate levels, a surrogate measure for maternal folate levels, and TL. We hypothesized that umbilical cord RBC folate concentrations would positively correlate with fetal TL. Data for this analysis were collected as part of a prospective cohort study that recruited pregnant women upon admission into labor and delivery. Cord blood was collected for 96 maternal-fetal dyads, and DNA analysis was performed using quantitative polymerase chain reaction. The telomere to single copy gene ratio method was used to determine TL, and RBC folate levels were measured. Statistical analysis was conducted by incorporating a bootstrapping approach into generalized linear modeling-based analyses. Consistent significant positive correlations were observed between RBC folate and TL (telomere to single copy gene ratio) with 9880 of the 10000 (98.8%) iterations performed having a P value less than .05. Our study shows a positive association between umbilical cord RBC folate and fetal TL at birth. These findings may provide a pathway of understanding and preventing adult-onset disease and mortality through intrauterine reprogramming.

Racial and ethnic disparities in U.S. breastfeeding and implications for maternal and child health outcomes

Marked racial and ethnic disparities exist in infant feeding in the United States. Based on a review of recent literature, this article examines current discrepancies between the 2020 Healthy People breastfeeding goals and current breastfeeding rates among women from different ethnic groups in the United States. We discuss maternal and child health outcomes associated with breastfeeding, and we review potential causes of racial and ethnic disparities in breastfeeding outcomes in the United States, especially among non-Hispanic Black, American Indian/Alaska Native, and Hispanic/Latina populations. We conclude with an overview of best practices in interventions aimed to increase U.S. breastfeeding rates, such as adoption of the baby friendly hospital initiative (BHFI) and programs that utilize peer counseling strategies to increase breastfeeding promotion and support.

Relationships of Feeding and Mother's Own Milk with Fecal Calprotectin Levels in Preterm Infants

OBJECTIVE To describe longitudinal effects of feeding volume and type of milk on fecal calprotectin (f-CP) in very low-birth weight (VLBW) infants. STUDY DESIGN Prospective data were collected across Neonatal Intensive Care Unit (NICU) admission for 6 weeks or until discharge in 75 VLBW neonates. The mean gestational age on entry into the study was 29 weeks. RESULTS Seventy-four (99%) mothers provided expressed milk in varying amounts. Twenty-three mothers (31%) provided exclusive mothers own milk (MOM) throughout. Preterm infant formula (PIF) and pasteurized donor milk were added to feedings of remaining infants. Pooled MOM was analyzed weekly for levels of a panel of cytokines, chemokines, and growth factors, and secretory Immunoglobulin A (sIgA) so that the exact amount of exposure to the gut of these milk bioactives could be estimated. f-CP levels ranged from 160 to 350 μg/g stool. Total feeding volume was positively associated with f-CP, controlling for infant weight, and f-CP levels rose across time. Exclusive MOM feedings for the entire measurement period were associated with rising levels of f-CP, but mixed feedings (MOM with added PIF or pasteurized donor milk (PDM) did not show this increase over time. CONCLUSION The presence of f-CP may represent a response to milk volumes and MOM, which represents normal development rather than always implicating pathological inflammation in the VLBW infant.

Homocysteine Levels Are not Related to Telomere Length in Cord Blood Leukocytes of Newborns.

Objective Elevated homocysteine (HC) levels and/or shortened telomere length (TL) are associated with adverse medical conditions. Our objective is to investigate the relationship between HC and TL in cord blood leukocytes of newborns. Study Design This is a nested study from a prospective cohort from 2011 to 2012 in pregnant women admitted for delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene ratio method was employed to quantify TL. Newborn HC levels were measured. generalized linear regression modeling (GLM) and bootstrap statistical analyses were performed. Results Seventy-seven maternal-fetal dyads with a mean gestational age of 39 weeks were included. The distribution of the coefficient of homocysteine showed most values greater than zero demonstrating that homocysteine had a positive relationship with TL. In 915 of 10,000 (9.15%) iterations, the p-value was < 0.05 demonstrating a positive effect. Conclusion Increasing newborn concentrations of HC are not associated with decreasing TL. Larger, prospective studies are needed to confirm these findings and long-term implications.

Prenatal diagnosis of aortopulmonary window associated with aberrant subclavian artery

Aortopulmonary window is a rare cardiac developmental anomaly characterised by a communication between the ascending aorta and the pulmonary artery. Aortopulmonary window may be isolated or associated with cardiac defects such as ventricular septal defect, atrial septal defect, interrupted aortic arch, and tetralogy of Fallot. We report a case of aortopulmonary window associated with aberrant subclavian artery based on fetal two-dimensional echocardiogram. The mother was referred for fetal echocardiography because of multiple fetal anomalies. Prenatal echocardiography at 30 weeks of gestation revealed a defect between the main and right pulmonary arteries and the ascending aorta (type III). The patient was born at 38 weeks of gestation via caesarean delivery, and was admitted to the neonatal intensive care unit because of respiratory failure and multiple congenital anomalies. Postnatal echocardiogram and cardiac MRI confirmed the prenatal findings. In addition, this patient had severe Dandy-Walker malformation and renal anomalies with poor prognosis. The family decided to withdraw respiratory care support on day of life 4, and the neonate passed away shortly after.

Prenatal Screening for Thrombophilias: Indications and Controversies, an Update

Pregnancy is associated with increased clotting potential and decreased fibrinolysis. Women with thrombophilias have an increased risk of venous thromboembolism during pregnancy. At least 50% of cases of venous thromboembolism in pregnant women are associated with an inherited or acquired thrombophilia. Acquired thrombophilias have also been linked with adverse pregnancy outcomes such as recurrent pregnancy loss, intrauterine fetal demise, early onset severe preeclampsia, placental abruption, and fetal growth restriction. This article addresses indications for thrombophilia testing, the appropriate laboratory tests, and timing of testing to ensure reliability of results.

Use of Commercial Tests for Aneuploidy Screening Using Cell-Free Fetal DNA in Clinical Practice

INTRODUCTION: The objective of this study was to characterize the use of the new commercial tests for aneuploidy screening using cell-free fetal DNA by women at high risk for fetal aneuploidy. METHODS: Retrospective cohort study of women undergoing cell-free fetal DNA testing in the first 6 months the tests were offered in our maternal-fetal medicine practice. All patients were high risk for fetal aneuploidy: advanced maternal age, abnormal aneuploidy screening, abnormal ultrasound findings, personal or family history, or all of these. Medical records were reviewed for patient demographics, indication for testing, pregnancy outcomes, and insurance information. RESULTS: One hundred forty-two patients underwent cell-free fetal DNA testing from January 1, 2012 to June 30, 2012. Mean maternal age was 32.3±6.5 years. Most patients were white (72%), non-Hispanic (83%), multiparous (64%), married (58%), had a private obstetrician (77%), had private insurance (52%), and were singleton gestations (95%). Median gestational age when the test was performed was 18 5/7 weeks. Four patients had positive test results (3%) and three had uninformative results (2%). There was one false-negative and no false-positive results. Sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 100%, 100%, and 99%, respectively. CONCLUSION: Our study provides some information on the use of new commercial tests for aneuploidy screening using cell-free fetal DNA in clinical practice in a nonresearch setting. Although the potential for these tests to provide women with information regarding their pregnancies without the risk of invasive testing is exciting, additional studies are needed to validate their performance in both low- and high-risk populations, and health care providers and patients need to be aware of their limitations.

145 – Smith-Lemli-Opitz Syndrome

Abstract Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in the gene encoding the 7-dehydrocholesterol reductase (7-DHC) resulting in decreased or absent function of this enzyme responsible for catalyzing the final step in cholesterol synthesis. Increased levels of 7-DHC and typically a reduction in cholesterol synthesis are seen in affected individuals. Diagnosis is made based on elevated 7-DHC. The estimated incidence of SLOS is 1 : 39,000 conceptions, with a carrier rate of approximately 1%. Higher carrier prevalence is reported in individuals of European or North American heritage. SLOS is characterized by growth failure, cognitive delay, behavioral disturbances, dysmorphic faces, and congenital defects. There is marked variability in the presentation of this condition ranging from mild effects that an individual remains undiagnosed, to fetal or neonatal death. The following findings on ultrasound (syndactyly/polydactyly, growth restriction, microcephaly, micrognathia, cleft palate, cardiac defects, and ambiguous male genitalia) in association with low maternal serum estriol and normal karyotype are highly suggestive of SLOS. Prenatal testing is available in at-risk pregnancies. Common postnatal therapies for SLOS include dietary cholesterol supplementation and surgical intervention, for the given defect or defects as appropriate.

Meckel-Gruber Syndrome

Abstract Meckel-Gruber syndrome is a severe ciliopathy first described in 1822. The worldwide incidence ranges from 1 : 1300 in Gujarati Indians to 1 : 140,000 in England. Twelve genetic mutations are associated with Meckel-Gruber syndrome (designated MKS1 through MKS12). In all cases, this disorder has shown autosomal recessive inheritance. The diagnosis of Meckel-Gruber syndrome is typically made by prenatal ultrasound examination in the first or second trimester. Meckel-Gruber syndrome is considered in an individual with a normal karyotype who has at least two of the three classic features: occipital encephalocele; large, polycystic kidneys; and postaxial polydactyly. Most affected individuals die in utero or mothers elect for termination of pregnancy. The postnatal mortality is 100% for individuals who survive to birth, with the longest survivor dying at 28 months. The major causes of death are pulmonary hypoplasia from oligohydramnios and liver disease.