Histologic chorioamnionitis in extremely preterm births, microbiological findings and infant outcome.

BACKGROUND: Histologic chorioamnionitis (HCA) is most often caused by ascending bacterial infection originating from the cervicovaginal tract. OBJECTIVES: To investigate whether HCA with a fetal inflammatory response (FIR) has a worse clinical outcome than HCA alone. Further, if FIR or a positive maternal microbiologic culture obtained prior to birth were related to adverse neonatal outcomes in a cohort of extremely preterm (EP) neonates. METHODS: Prospective observational cohort study recruiting EP singleton pregnancies (gestational age at birth ≤28 weeks) with confirmed HCA. FIR was defined by fetal neutrophils in the chorionic vessels and/or umbilical vessels. Positive culture was defined as growth of potentially pathogenic bacteria in a sample from the cervicovaginal tract prior to birth, or if a cervicovaginal culture was lacking, a culture result from the placenta was used. Logistic regression was used to estimate odds ratios and 95% confidence intervals for the associations between FIR, a positive culture result and adverse outcomes, defined as bronchopulmonary dysplasia (BPD), brain pathology assessed by magnetic resonance imaging, retinopathy of prematurity, necrotizing enterocolitis, early-onset neonatal sepsis, and perinatal death. A composite outcome variable included one or more adverse outcomes. RESULTS: We included 71 cases with HCA, of which 51 (72%) had FIR. Maternal age, rate of clinical chorioamnionitis (CCA), preterm pre-labor rupture of membranes (PPROM), the number of women receiving antenatal steroids and antibiotics, and the rate of positive maternal cultures of potentially pathogenic bacteria were all significantly higher in the HCA with FIR. Neonates in the FIR group had significantly higher levels of blood leukocytes compared to those without. FIR was associated with a longer interval from PPROM to delivery (log-rank test: p = .022). Microbiological sampling had been performed in 63 (89%) cases, of which 60 (95%) were cervicovaginal samples. No associations were found between a positive culture and adverse neonatal outcomes, in contrast to FIR, that was significantly associated to BPD and brain pathology. CONCLUSIONS: In a cohort of EP pregnancies with confirmed HCA, the presence of FIR was associated with advanced maternal age, CCA, PPROM, antenatal steroids and antibiotics, and a positive maternal culture of potentially pathogenic bacteria. However, the presence of FIR, and not a positive culture, was associated with adverse neonatal outcomes.

The outcome of pregnancies after bariatric surgery: an observational study of pregnancies during 2004-2016 in Finland.

PURPOSE: Overweight and obesity are major risk factors for perinatal morbidity and mortality, and the need for bariatric surgery (BS) among fertile-aged women is increasing. This study evaluates the outcome of post-BS pregnancies and deliveries. METHODS: All 20-45-year-old patients delivering between 2004 and 2016 in Finland were included. Patients with previous BS were identified from the hospital discharge register, and the medical birth register was queried for data on pregnancies, deliveries, and perinatal outcomes. The data were matched using personal identification codes, and the outcomes of women with previous BS were compared with those of other pregnancies. RESULTS: Women with previous BS (n = 314) constituted the bariatric group. When compared with the non-bariatric group (n = 750,019), they were older (p < 0.001), heavier (p < 0.001) and had more previous pregnancies (p < 0.001). The overall incidence of pregnancy-induced hypertension (p = 0.002), gestational diabetes (GDM) (p = 0.018), pre-term contractions (p = 0.023), pre-term delivery (p = 0.003), labour induction (p < 0.001), planned (p = 0.001) and unplanned (p = 0.036) caesarean sections and low birthweight infants (p < 0.001) were significantly higher in the bariatric group. When compared with body mass index-specific categories, the main outcomes were increased incidence of GDM and small for gestational age (SGA) newborns in the bariatric group. CONCLUSION: BS can be considered a safe and advisable treatment for obesity among fertile-aged women. The pregnancy outcome is associated with post-BS weight, but the risk for GDM and small for gestational-age newborns is increased.

Neonatal Gastric Perforation: 14-Year Experience from a Tertiary Neonatal Intensive Care Unit.

OBJECTIVE: Neonatal gastric perforations (NGPs) are rare and account for 7 to 12% of all gastrointestinal perforations in the neonatal period. The etiology and prognostic factors associated with NGP remain unclear. The aim of this study is to review the cases of NGP in our neonatal intensive care unit (NICU) in the past 14 years and describe the risk factors, clinical presentation, and outcomes associated with it. STUDY DESIGN: A retrospective chart review of neonates with gastric perforation admitted to the NICU between June 2006 and December 2020 was performed. Data regarding their antenatal and neonatal characteristics, laboratory and radiological results, intra-operative findings, hospital course, and outcomes were recorded. RESULTS: We identified 350 patients with gastrointestinal perforation at our center during the study period of which 14 (4%; nine males and five females) patients were diagnosed with NGP during surgery. A total of 71% neonates were born preterm (range: 24-39 weeks, median: 34 weeks). Two neonates (14%) were SGA. Only one neonate received cardiopulmonary resuscitation at birth. In all neonates, except two, perforation occurred within the first 10 days of life (median: 4 days, range: 1-22 days). In total, 79% infants received feeds prior to perforation. Ten neonates had a feeding tube, and one neonate had a gastrostomy tube placed prior to perforation. Abdominal distension and pneumoperitoneum were present in all neonates. Majority of the babies had metabolic acidosis (64%) and elevated C-reactive protein (79%). Most (86%) neonates received surgical intervention within 12 hours. Overall survival in our study was 93%. CONCLUSION: NGP is a rare entity seen mostly in preterm infants within the first 10 days of life. Clinical presentation is similar to perforation anywhere along the gastrointestinal tract and definite diagnosis requires exploratory laparotomy. With prompt recognition and surgical intervention, the overall mortality related to neonatal gastric perforation is low. KEY POINTS: · Neonatal gastric perforation is a rare but life threatening entity with unclear etiology.. · Prematurity is associated with an increased incidence of gastric perforations in the neonate.. · Laparotomy is required for definitive diagnosis and treatment..

Hipoglucemia neonatal en hijos de madres con diabetes mellitus gestacional. Comparación de la incidencia según el tratamiento materno / Neonatal hypoglycemia in infants born to mothers with gestational diabetes mellitus. Comparison of its incidence based on maternal treatment

Introducción. La hipoglucemia neonatal es una complicación de la diabetes mellitus gestacional Son pocos los estudios que avalan la pesquisa sistemática en este grupo poblacional durante las primeras horas de vida. Objetivos. Evaluar la asociación entre tratamiento materno recibido (dieta versus insulina) y el desarrollo de hipoglucemia, e identificar los factores de riesgo asociados. Población y métodos. Estudio observacional, analítico y retrospectivo realizado en en las sedes de Buenos AIres y San Justo de un hospital general de tercer nivel entre el 1 de enero de 2017 y el 31 de diciembre de 2018. Se estimó la incidencia de hipoglucemia (≤47 mg/dl) en recién nacidos según el manejo de la diabetes materna y se realizó un análisis multivariable para evaluar factores asociados. Resultados. Se incluyeron 195 pacientes. No se encontró diferencia estadística en la incidencia de hipoglucemia según el tratamiento materno recibido (45,3 % versus 39,7 %; p = 0,45) ni se identificaron factores de riesgo asociados. Modificando el valor de corte a ≤40 mg/dl, tampoco se encontraron diferencias en la incidencia (23,4 % versus 19 %, p = 0,48); no obstante, los pacientes hipoglucémicos presentaron un hematocrito significativamente mayor y una menor prevalencia de lactancia exclusiva al egreso. El análisis multivariable mostró una asociación independiente entre alto peso al nacer con hipoglucemia que requiere corrección. Conclusiones. La incidencia de hipoglucemia neonatal en la población estudiada no presentó diferencia según el tratamiento materno recibido. El estudio realizado fundamenta el control de la glucemia en estos niños en la práctica diaria.

Introduction. Neonatal hypoglycemia is a complication of gestational diabetes mellitus. Few studies have been conducted to support a systematic screening in the first hours of life of this population group. Objectives. To assess the association between the treatment administered to the mother (diet vs. insulin) and the development of hypoglycemia, and to identify associated risk factors. Population and methods. Observational, analytical, and retrospective study carried out at the Buenos Aires and San Justo maternal centers of a general, tertiary care hospital between 01-01-2017 and 12-31-2018. The incidence of neonatal hypoglycemia (≤ 47 mg/dL) based on the management of maternal diabetes was estimated and a multivariate analysis was done to assess related factors. Results. A total of 195 patients were included. No statistical difference was found in the incidence of hypoglycemia based on the treatment administered to the mother (45.3% vs. 39.7%; p = 0.45) and no associated risk factors were identified. Once the cutoff point was changed to ≤ 40 mg/dL, no differences were found in the incidence either (23.4% versus 19%, p = 0.48); however, patients with hypoglycemia had a significantly higher hematocrit level and a lower prevalence of exclusive breastfeeding upon discharge. Multivariate analysis showed an independent association between a high birth weight and hypoglycemia, requiring correction. Conclusions. The incidence of neonatal hypoglycemia in the studied population did not vary based on the treatment received by the mother. This study supports the control of glycemia in these infants in daily practice.

Neonatal Thrombocytopenia Due to Dual Alloimmune and Autoimmune Mechanisms.

Alloantibody-mediated and autoantibody-mediated immune destruction are common causes of early neonatal thrombocytopenia. The authors report a case of severe, early-onset thrombocytopenia with mucocutaneous bleeding in an otherwise well-appearing full-term neonate. Recurrence of thrombocytopenia following initial treatment and its persistence after 2 weeks of life suggested a dual immune mechanism. This is a rare case of immune thrombocytopenia caused by human platelet antigen-5b alloimmunization and passive transfer of maternal antiplatelet antibodies. Appropriate, timely treatment and absence of severe bleeding complications, namely intracranial hemorrhage, conferred a good overall prognosis.

Eclampsia in the 21st century.

The reported incidence of eclampsia is 1.6 to 10 per 10,000 deliveries in developed countries, whereas it is 50 to 151 per 10,000 deliveries in developing countries. In addition, low-resource countries have substantially higher rates of maternal and perinatal mortalities and morbidities. This disparity in incidence and pregnancy outcomes may be related to universal access to prenatal care, early detection of preeclampsia, timely delivery, and availability of healthcare resources in developed countries compared to developing countries. Because of its infrequency in developed countries, many obstetrical providers and maternity units have minimal to no experience in the acute management of eclampsia and its complications. Therefore, clear protocols for prevention of eclampsia in those with severe preeclampsia and acute treatment of eclamptic seizures at all levels of healthcare are required for better maternal and neonatal outcomes. Eclamptic seizure will occur in 2% of women with preeclampsia with severe features who are not receiving magnesium sulfate and in <0.6% in those receiving magnesium sulfate. The pathogenesis of an eclamptic seizure is not well understood; however, the blood-brain barrier disruption with the passage of fluid, ions, and plasma protein into the brain parenchyma remains the leading theory. New data suggest that blood-brain barrier permeability may increase by circulating factors found in preeclamptic women plasma, such as vascular endothelial growth factor and placental growth factor. The management of an eclamptic seizure will include supportive care to prevent serious maternal injury, magnesium sulfate for prevention of recurrent seizures, and promoting delivery. Although routine imagining following an eclamptic seizure is not recommended, the classic finding is referred to as the posterior reversible encephalopathy syndrome. Most patients with posterior reversible encephalopathy syndrome will show complete resolution of the imaging finding within 1 to 2 weeks, but routine imaging follow-up is unnecessary unless there are findings of intracranial hemorrhage, infraction, or ongoing neurologic deficit. Eclampsia is associated with increased risk of maternal mortality and morbidity, such as placental abruption, disseminated intravascular coagulation, pulmonary edema, aspiration pneumonia, cardiopulmonary arrest, and acute renal failure. Furthermore, a history of eclamptic seizures may be related to long-term cardiovascular risk and cognitive difficulties related to memory and concentration years after the index pregnancy. Finally, limited data suggest that placental growth factor levels in women with preeclampsia are superior to clinical markers in prediction of adverse pregnancy outcomes. This data may be extrapolated to the prediction of eclampsia in future studies. This summary of available evidence provides data and expert opinion on possible pathogenesis of eclampsia, imaging findings, differential diagnosis, and stepwise approach regarding the management of eclampsia before delivery and after delivery as well as current recommendations for the prevention of eclamptic seizures in women with preeclampsia.

Estado nutricional de la mujer embarazada y su relación con las complicaciones de la gestación y el recién nacido / Nutrition status of pregnant women and its relationship with complications of pregnancy and the newborn

RESUMEN: El estado nutricional materno determina las condiciones de salud y nutricionales del recién nacido, así como las complicaciones durante el embarazo y el parto. Se realizó el estudio en 894 mujeres que tuvieron su parto en los Hospitales de la ciudad de Loja Ecuador durante el periodo enero - junio del 2019. Se determinó la antropometría de la madre y de su hijo, así como se tomó datos de complicaciones durante el embarazo y el parto, de su historia clínica. Además, se efectuó la correlación entre el estado nutricional pre-gestacional de la madre con el recién nacido, de igual forma con el estado de salud de la madre. El objetivo de este trabajo fue determinar el estado nutricional pre-gestacional y su relación con la condición de salud y nutricional del niño. El IMC pre-gestacional reportó 47,3 % de sobrepeso y obesidad y 2,6 % de bajo peso. En un porcentaje mayor al 10 % las madres con sobrepeso y obesidad tuvieron hijos grandes para la edad gestacional, de igual forma las madres con bajo peso tuvieron el 26,1 % recién nacidos pequeños. Las principales complicaciones de las madres relacionadas con sobrepeso y obesidad fueron: diabetes gestacional, hemorragia postparto y pre-eclampsia durante el embrazo. Importante señalar la alta frecuencia de infecciones de las vías urinarias 53,9 % (478); y vaginitis 22,3 % (199); aunque estas no están directamente relacionadas con procesos metabólicos como etiología, más si están favorecidos por ellos. Durante el parto la complicación más frecuente fue el parto distócico con un 8,9 % (77), además del total de partos el 41,8 % (374) terminaron en cesárea, de estos el 51, 6 % (193) corresponden a sobrepeso y obesidad. Las complicaciones del recién nacido fueron: Síndrome de dificultad respiratoria aguda, asfixia neonatal e hipoglicemia. En conclusión, el estado nutricional pre-gestacional de la madre está relacionado directamente con el estado de salud y nutricional del recién nacido.

SUMMARY: The maternal nutritional status determines the health and nutritional conditions of the newborn, as well as complications during pregnancy and childbirth. The study was carried out in 894 women who had their delivery in the Hospitals of the city of Loja Ecuador during the period January - June 2019. The anthropometry of the mother and her child was determined, as well as data on complications during pregnancy and delivery, from their clinical history. In addition, the correlation was made between the pre-gestational nutritional status of the mother with the newborn, in the same way with the health status of the mother. The objective of this work was to determine the pre-gestational nutritional status and its relationship with the health and nutritional condition of the child. The pre-gestational BMI reported 47.3 % overweight and obesity and 2.6 % underweight. In a percentage higher than 10 %, mothers with overweight and obesity had large children for gestational age, in the same way, mothers with low weight had 26.1 % small newborns. The main complications of the mothers related to overweight and obesity were: gestational diabe- tes, postpartum hemorrhage and pre-eclampsia during pregnancy. It is important to note the high frequency of urinary tract infections 53.9% (478); and vaginitis 22.3% (199; although these are not directly related to metabolic processes such as etiology, more if they are favored by them. During delivery, the most frequent complication was dystocic delivery with 8.9 % (77), in addition to the total deliveries 42.5 % (374) that ended in cesarean section, of which 51.6 % (193) correspond to overweight and obesity. The complications of the newborn were: Acute respiratory distress syndrome, neonatal asphyxia and hypoglycemia. In conclusion, the pre-gestational nutritional status of the mother is directly related to the health and nutritional status of the newborn.

Maternal smoking behaviour across the first two pregnancies and small for gestational age birth: Analysis of the SLOPE (Studying Lifecourse Obesity PrEdictors) population-based cohort in the South of England.

Maternal smoking is established to cause adverse birth outcomes, but evidence considering maternal smoking change across successive pregnancies is sparse. We examined the association between self-reported maternal smoking during and between the first two pregnancies with the odds of small for gestational age (SGA) birth (<10th percentile) in the second infant. Records for the first two pregnancies for 16791 women within the SLOPE (Studying Lifecourse Obesity PrEdictors) study were analysed. This is a population-based cohort of prospectively collected anonymised antenatal and birth healthcare data (2003-2018) in Hampshire, UK. Logistic regression was used to relate maternal smoking change to the odds of SGA birth in the second infant. In the full sample, compared to never smokers, mothers smoking at the start of the first pregnancy had higher odds of SGA birth in the second pregnancy even where they stopped smoking before the first antenatal appointment for the second pregnancy (adjusted odds ratio (aOR) 1.50 [95% confidence interval 1.10, 2.03]). If a mother was not a smoker at the first antenatal appointment for either her first or her second pregnancy, but smoked later in her first pregnancy or between pregnancies, there was no evidence of increased risk of SGA birth in the second pregnancy compared to never smokers. A mother who smoked ten or more cigarettes a day at the start of both of her first two pregnancies had the highest odds of SGA birth (3.54 [2.55, 4.92]). Women who were not smoking at the start of the first pregnancy but who subsequently resumed/began smoking and smoked at the start of their second pregnancy, also had higher odds (2.11 [1.51, 2.95]) than never smokers. Smoking in the first pregnancy was associated with SGA birth in the second pregnancy, even if the mother quit by the confirmation of her second pregnancy.

The association of low body mass index with neonatal morbidities in preterm infants.

Little is known about the association between body proportionality at birth and neonatal outcomes in preterm infants. Body mass index (BMI) is one of the weigh-for-length ratios that represent body proportionality. The objective of this study was to examine whether BMI at birth affects neonatal outcomes in preterm infants. We assessed 3115 preterm (< 30 weeks), very low birth weight (< 1500 g) infants born between January 2013 and December 2016 and registered in the Korean Neonatal Network database. Using gender-specific BMI for gestational age curves, z-scores of BMI at birth were calculated. Low-, normal-, and high-BMI were defined as BMI z-scores of less than - 1, from - 1 to 1, and greater than 1, respectively. Neonatal morbidities and mortality in low- and high-BMI groups were compared to those in normal-BMI group. The low-BMI group had an increased risk of bronchopulmonary dysplasia, bronchopulmonary dysplasia or death, and necrotizing enterocolitis after adjusting for baseline characteristics and the birth weight z-score. High-BMI group had comparable neonatal outcomes to those of normal-BMI group. Low BMI at birth was associated with an increased risk of bronchopulmonary dysplasia and necrotizing enterocolitis, whereas High BMI at birth was not associated with adverse neonatal outcomes.

A retrospective, observational study of medicolegal cases against obstetricians and gynaecologists in South Africa's private sector.

BACKGROUND:  The viability of obstetric practice in the private sector has been threatened as a result of steep increases in professional indemnity fees over the past 10 years. Despite this, empirical research investigating key aetiological factors to target risk management interventions has been lacking. OBJECTIVES: To explore private practice medicolegal data linked to obstetricians and gynaecologists (O&Gs) to identify factors in clinical practice associated with claims, for the purposes of guiding future research and risk management solutions. METHODS:  This was a retrospective, observational study of private sector O&Gs' medicolegal case histories. All incidents declared to a prominent local professional indemnity insurer were categorised in terms of medicolegal case type, as well as clinical parameters. To allow for risk-adjusted calculations of case incidence, year of entry into private practice was estimated for all practitioners. RESULTS:  Steep increases in medicolegal investigations and demands were demonstrated for both obstetrics- and gynaecology-related cases from about 2003 to 2012. Whereas the total numbers of claims, regulatory complaints and requests for records were similar for obstetrics and gynaecology in recent years (accounting for 52% v. 48% of known cases, respectively), a significantly greater percentage of demands and paid settlements related to gynaecology rather than obstetrics (58% and 76% v. 42% and 24% of cases, respectively). In obstetrics, about half of all cases on record with a paid settlement were in the context of severe neonatal birth-related neurological injury (n=9). For gynaecology, procedure-related complications accounted for 92% of settlements, of which at least 41% were for intraoperative injuries to internal organs and vessels. Laparoscopic procedures were most frequently associated with such intraoperative injuries, followed by vaginal and abdominal hysterectomies/oophorectomies and caesarean sections. For O&Gs in private practice for >2 years, 50/458 (11%) accounted for 138/228 (61%) of demands over a 10-year period. CONCLUSIONS:  The higher number of gynaecological demands and settlements in comparison with obstetric cases was unexpected and is contrary to international experiences and public sector findings, calling for more research to identify reasons for this finding. Other than further exploring surgical outcomes in private sector gynaecological patients, aspects of surgical training and accreditation standards in gynaecology may need review. Regarding birth-related injuries, the contribution of system failures needs quantification and further interrogation. The high contribution towards the medicolegal burden by a small group of practitioners suggests a need for doctor-focused interventions, including strengthening of peer review and regulatory oversight.

Case Report: Neonatal Diabetes Mellitus Caused by a Novel GLIS3 Mutation in Twins.

Background: Mutations in GLIS3 cause a rare syndrome characterized by neonatal diabetes mellitus (NDM), congenital hypothyroidism, congenital glaucoma and cystic kidneys. To date, 14 mutations in GLIS3 have been reported, inherited in an autosomal recessive manner. GLIS3 is a key transcription factor involved in ß-cell development, insulin expression, and development of the thyroid, eyes, liver and kidneys. Cases: We describe non-identical twins born to consanguineous parents presenting with NDM, congenital hypothyroidism, congenital glaucoma, hepatic cholestasis, cystic kidney and delayed psychomotor development. Sequence analysis of GLIS3 identified a novel homozygous nonsense mutation, c.2392C>T, p.Gln798Ter (p.Q798*), which results in an early stop codon. The diabetes was treated with a continuous subcutaneous insulin infusion pump and continuous glucose monitoring. Fluctuating blood glucose and intermittent hypoglycemia were observed on follow-up. Conclusions: This report highlights the importance of early molecular diagnosis for appropriate management of NDM. We describe a novel nonsense mutation of GLIS3 causing NDM, extend the phenotype, and discuss the challenges in clinical management. Our findings provide new areas for further investigation into the roles of GLIS3 in the pathophysiology of diabetes mellitus.

Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: A pilot randomised placebo-controlled trial.

BACKGROUND: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257). METHODS: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events. FINDINGS: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment. INTERPRETATION: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome. FUNDING: Health Research Council of New Zealand, A Better Start - National Science Challenge.

Short- and Long-Term Outcomes Associated with Large for Gestational Age Birth Weight.

Large for gestational age birth weight is associated with adverse short- and long-term outcomes. Infants born with large for gestational age birth weight are at increased risk for neonatal intensive care unit admission, respiratory distress, neonatal metabolic abnormalities including hypoglycemia, birth trauma, and even stillbirth or neonatal death. The risk for many of these complications increases with higher birth weights. Individuals with large for gestational age birth weight also appear to be at subsequent increased risk for overweight/obesity, diabetes, cardiovascular disease, and even some childhood cancers. These data highlight the need for effective interventions to decrease risk across the lifespan.

Associations of ultrasound estimated early mid pregnancy visceral and subcutaneous fat depths and early pregnancy BMI with adverse neonatal outcomes.

This study investigated whether maternal central adiposity and body mass index (BMI) were associated with neonatal hypoglycemia and adverse neonatal outcomes. A cohort study was performed at Uppsala University Hospital, Sweden, between 2015 and 2018. Visceral and subcutaneous fat depths were measured by ultrasound at the early second-trimester anomaly scan in 2771 women giving birth to singleton infants. Body mass index was assessed in early pregnancy. Logistic regression models were performed. Adjustments were made for age, BMI (not in model with BMI as exposure), smoking, maternal country of birth, and parity. Outcomes were neonatal hypoglycemia (blood glucose concentration < 2.6 mmol/l), a composite of adverse neonatal outcomes (Apgar < 7 at 5 min of age, or umbilical artery pH ≤ 7.0, or admission to neonatal intensive care unit), and the components of the composite outcome. Visceral and subcutaneous fat depths measured by ultrasound in early mid pregnancy were not associated with any of the outcomes in adjusted analyses. For every unit increase in BMI, the likelihood of neonatal hypoglycemia increased by 5% (aOR 1.05, 95% CI 1.01-1.10), the composite outcome by 5% (aOR 1.05, 95% CI 1.01-1.08), and admission to neonatal intensive care unit by 6% (aOR 1.06, 95% CI 1.02-1.10).

Maternal and fetal outcomes in phaeochromocytoma and pregnancy: a multicentre retrospective cohort study and systematic review of literature.

BACKGROUND: Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. METHODS: We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression. FINDINGS: The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery). INTERPRETATION: Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. FUNDING: US National Institutes of Health.

Reproductive technologies, female infertility, and the risk of imprinting-related disorders.

BACKGROUND: Epidemiological studies suggest that singletons born from assisted reproductive technologies (ART) have a high risk of adverse perinatal outcomes, specifically for imprinting disorders. Because ART processes take place at times when epigenetic reprogramming/imprinting are occurring, there is concern that ART can affect genomic imprints. However, little is currently known about the risk of imprinting defects according to the type of ART or the type of underlying female infertility. From the French national health database, a cohort of 3,501,495 singletons born over a 5-year period (2013-2017) following fresh embryo or frozen embryo transfers (fresh-ET or FET from in vitro fertilization), intrauterine insemination, or natural conception was followed up to early childhood. Based on clinical features, several syndromes/diseases involving imprinted genes were monitored. The effects of ART conception and the underlying cause of female infertility were assessed. RESULTS: Compared with infants conceived naturally, children born after fresh-ET had a higher prevalence of imprinting-related diseases, with an aOR of 1.43 [95% CI 1.13-1.81, p = 0.003]. Namely, we observed an increased risk of neonatal diabetes mellitus (1.96 aOR [95% CI 1.43-2.70], p < 0.001). There was an overall independent increase in risk of imprinting diseases for children with mothers diagnosed with endometriosis (1.38 aOR [95% CI 1.06-1.80], p = 0.02). Young and advanced maternal age, primiparity, obesity, smoking, and history of high blood pressure or diabetes were also associated with high global risk. CONCLUSIONS: This prospective epidemiological study showed that the risk of clinically diagnosed imprinting-related diseases is increased in children conceived after fresh embryo transfers or from mothers with endometriosis. The increased perturbations in genomic imprinting could be caused by controlled ovarian hyperstimulation and potentially endometriosis through the impairment of endometrial receptivity and placentation, leading to epigenetic feto-placental changes. Further studies are now needed to improve understanding of the underlying molecular mechanisms (i.e. genetic or epigenetic causes).

Risk stratification for small for gestational age for the Brazilian population: a secondary analysis of the Birth in Brazil study.

Risk-stratification screening for SGA has been proposed in high-income countries to prevent perinatal morbidity and mortality. There is paucity of data from middle-income settings. The aim of this study is to explore risk factors for SGA in Brazil and assess potential for risk stratification. This population-based study is a secondary analysis of Birth in Brazil study, conducted in 266 maternity units between 2011 and 2012. Univariate and multivariate logistic regressions were performed, and population attributable fraction estimated for early and all pregnancy factors. We calculated absolute risk, odds ratio, and population prevalence of single or combined factors stratified by parity. Factors associated with SGA were maternal lupus (ORadj 4.36, 95% CI [2.32-8.18]), hypertensive disorders in pregnancy (ORadj 2.72, 95% CI [2.28-3.24]), weight gain < 5 kg (ORadj 2.37, 95% CI [1.99-2.83]), smoking at late pregnancy (ORadj 2.04, 95% CI [1.60-2.59]), previous low birthweight (ORadj 2.22, 95% CI [1.79-2.75]), nulliparity (ORadj 1.81, 95% CI [1.60-2.05]), underweight (ORadj 1.61, 95% CI [1.36-1.92]) and socioeconomic status (SES) < 5th centile (ORadj 1.23, 95% CI [1.05-1.45]). Having two or more risk factors (prevalence of 4.4% and 8.0%) was associated with a 2 and fourfold increase in the risk for SGA in nulliparous and multiparous, respectively. Early and all pregnancy risk factors allow development of risk-stratification for SGA. Implementation of risk stratification coupled with specific strategies for reduction of risk and increased surveillance has the potential to contribute to the reduction of stillbirth in Brazil through increased detection of SGA, appropriate management and timely delivery.

Elevated maternal androgen is associated with dysfunctional placenta and lipid disorder in newborns of mothers with polycystic ovary syndrome.

OBJECTIVE: To investigate the placental morphology alterations and identify the clinical characteristics of women with polycystic ovary syndrome (PCOS) and their newborns. Pregnant women with PCOS (n = 12) and pregnant women without PCOS (n = 11) were recruited. Then, the placenta, maternal blood and cord blood were collected after delivery. DESIGN: Clinical observational study. SETTING: Not applicable. PATIENT(S): In the present study, pregnant women with PCOS and healthy pregnant women were recruited from the clinic of the Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, China, between February 2015 and October 2015. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A proteomic analysis was performed on the placenta in women with PCOS and healthy women. RESULT(S): The maternal testosterone, androstenedione, dehydroepiandrosterone sulfate, free androgen index, cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A-I levels were significantly higher in the PCOS group than in the control group, and the offspring in the PCOS group had higher dehydroepiandrosterone sulfate, high-density lipoprotein, and cholesterol levels, when compared with the control group. The placenta in the PCOS group demonstrated infarction, calcification, and a greater intervillous space, when compared with the control group. A higher level of estrogen receptor-ß protein was observed in the placenta of women with PCOS, when compared with women without PCOS. A total of 258 proteins in the placenta were identified to be significantly different, when the PCOS and control groups were compared, and fibronectin 1 exhibited the closest relationship with other differential proteins. CONCLUSION(S): The overexposure to hyperandrogenism and hyperlipidemia affects the functions of the placenta, which are associated with the development of metabolic disorders in newborns.

Association between endometrial thickness and neonatal outcomes in intrauterine insemination cycles: a retrospective analysis of 1,016 live-born singletons.

BACKGROUND: Decreased endometrial thickness (EMT) has been suggested to be associated with reduced birthweight of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) newborns. Considering the differences in ovarian stimulation degree and laboratory procedures between IVF/ICSI and IUI treatment, we aim to investigate whether EMT has any influence on IUI infant outcomes as well. METHODS: This was a retrospective cohort study of 1016 patients who had singleton livebirths after IUI treatment cycles from January 2008 to December 2018 at a tertiary-care academic medical center in China. Patients were categorized into three groups by the 10th and 90th percentile of peak EMT: ≤7.6, 7.7-13.0 and ≥ 13.1 mm. The primary outcomes of the study were preterm birth (PTB), low birthweight (LBW) and small-for-gestational age (SGA). Multiple regression analyses were performed after controlling for a variety of potential confounders. RESULTS: No significant differences were found among the three groups in gestational age, birthweight and birthweight Z-score. Compared with the EMT 7.7-13.0 mm group, the incidences of PTB, LBW and SGA were 5.5% (adjusted odds ratio [aOR] 0.81, 95% confidence interval [CI] 0.33-2.01), 6.4% (aOR 1.44, 95% CI 0.58-3.58) and 7.3% (aOR 1.21, 95% CI 0.53-2.76) in the EMT ≤7.6 mm group, respectively. Similarly, EMT ≥13.1 mm was not significantly associated with risks of PTB (aOR 0.63, 95% CI 0.24-1.65), LBW (aOR 0.57, 95% CI 0.17-1.95) and SGA (aOR 0.73, 95% CI 0.28-1.92). The odds of other adverse neonatal outcomes, including macrosomia, large-for-gestational age and major congenital malformations, did not show significant differences before and after adjustment in both EMT ≤7.6 and ≥ 13.1 mm groups. CONCLUSIONS: EMT is not independently associated with adverse perinatal outcomes in IUI cycles. This novel finding would provide reassuring information for IUI patients with thin endometrial linings regarding their neonatal health. However, further prospective cohort studies with larger datasets are needed to confirm the conclusion.

Neonatal Vocal Fold Paralysis.

Vocal fold paralysis (VFP) is an important cause of respiratory and feeding compromise in infants. The causes of neonatal VFP are varied and include central nervous system disorders, birth-related trauma, mediastinal masses, iatrogenic injuries, and idiopathic cases. Bilateral VFP often presents with stridor or respiratory distress and can require rapid intervention to stabilize an adequate airway. Unilateral VFP presents more subtly with a weak cry, swallowing dysfunction, and less frequently respiratory distress. The etiology and type of VFP is important for management. Evaluation involves direct visualization of the vocal folds, with additional imaging and testing in select cases. Swallowing dysfunction, also known as dysphagia, is very common in infants with VFP. A clinical assessment of swallowing function is necessary in all cases of VFP, with some patients also requiring an instrumental swallow assessment. Modification of feeding techniques and enteral access for feedings may be necessary. Airway management can vary from close monitoring to noninvasive ventilation, tracheostomy, and laryngeal surgery. Long-term follow-up with otolaryngology and speech-language pathology service is necessary for all children with VFP to ensure adequate breathing, swallowing, and phonation. The short- and long-term health and quality-of-life consequences of VFP can be substantial, especially if not managed early.