Objectif: La prématurité a lieu pendant une période critique de la minéralisation osseuse. Nous avons évalué si la naissance prématurée se traduit par un risque plus élevé de fracture orthopédique chez les enfants. Méthodes: Nous avons mené une étude de cohorte rétrospective sur 788 903 enfants nés entre 2006 et 2016 au Québec, Canada, avec 5 436 400 personnes-années de suivi. Nous avons distingué les enfants nés prématurés (<37 semaines) et nés à terme (≥ 37 semaines). Nous avons identifié les hospitalisations futures pour fractures osseuses nécessitant un traitement chirurgical avant 2018. Nous avons calculé les taux d'incidence et les hazard ratios estimés (HR) avec des intervalles de confiance (IC) à 95% pour mesurer l'association entre la prématurité et les fractures à l'aide de modèles de régression de Cox ajustés pour les caractéristiques de l’enfant et maternelles. Nous avons déterminé si le risque de fracture variait en fonction de l'âge de l'enfant. Résultats: Il y avait 51 212 nouveau-nés prématurés dans cette étude (6,5%). L'incidence de fracture était de 17,9 par 10 000 personnes-années chez les enfants prématurés et de 15,3 par 10 000 personnes-années pour les enfants nés à terme. Comparativement aux enfants nés à terme, les enfants prématurés présentaient un risque de fracture 1,08 fois plus élevé lors du suivi (IC 95% 0,99-1,18). Les associations étaient plus fortes pour le fémur (HR 1,27, IC 95% 1,01-1,60) et les fractures liées à une agression (HR 2,27, IC 95% 1,37-3,76). Les associations variaient également avec l'âge, les enfants prématurés ayant deux fois le risque de fracture du fémur entre 6 et 17 mois (HR 2,20, IC 95% 1,45-3,35), mais aucune association par la suite. Conclusion: La prématurité est associée à un risque accru de certaines fractures osseuses et de fractures liées à des agressions avant l'âge de 18 mois. Les familles d'enfants prématurés pourraient bénéficier de conseils et de soutien pour la prévention des fractures au cours de la petite enfance. / Objective: Preterm birth occurs during a critical period of bone mineralization. We assessed whether preterm birth translates into a higher risk of orthopedic fracture in childhood. Methods: We conducted a retrospective cohort study of 788,903 infants born between 2006 and 2016 in Quebec, Canada, including 5,436,400 person-years of follow-up. We distinguished preterm (<37 weeks) and term (≥37 weeks) infants and identified future hospitalizations for bone fractures that required operative treatment before 2018. We calculated incidence rates and estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of prematurity with fractures using Cox regression models adjusted for maternal and infant characteristics. We determined if the risk of fracture varied by the child’s age. Results: There were 51,212 preterm infants in this study (6.5%). The incidence of fracture was 17.9 per 10,000 person-years in preterm children and 15.3 per 10,000 person-years in term children. Compared with term, preterm children had 1.08 times the risk of fracture during follow-up (95% CI 0.99-1.18). Associations were stronger for femur (HR 1.27, 95% CI 1.01-1.60) and assault-related fractures (HR 2.27, 95% CI 1.37-3.76). Associations also varied with age, with preterm children having 2 times the risk of femur fracture between 6 and 17 months of age (HR 2.20, 95% CI 1.45-3.35), but no association thereafter. Conclusion: Preterm birth is associated with an increased risk of certain bone fractures and assault-related fractures before 18 months of age. Families of preterm children may benefit from counselling and support for fracture prevention during early childhood.

Le retard de croissance intra-utérin (RCIU) est une complication responsable d’une importante mortalité et morbidité périnatales. Son dépistage représente un enjeu important de la surveillance prénatale. Les objectifs de la thèse étaient d’évaluer la performance du dépistage anténatal du RCIU, d’identifier ses déterminants et de mesurer son impact sur les issues périnatales. Dans une première partie, nous avons utilisé les données de l’Enquête Nationale Périnatale de 2010 (N=14 100 enfants uniques) : 21,7% des enfants de poids <10ème percentile étaient suspectés avec un RCIU en anténatal tandis que la moitié des enfants suspectés avait un poids normal à la naissance (faux positifs). Le risque de naissance induite était élevé en cas de suspicion, indépendamment de l’existence d’un faible poids, suggérant des interventions iatrogènes. Les issues néonatales n’étaient pas différentes selon la suspicion. Dans une seconde partie, nous avons utilisé les données d’une cohorte nationale d’enfants nés avant 32 SA en 2011, EPIPAGE 2 (N=3698 enfants uniques sans anomalie congénitale). La prise en charge active pour indication fœtale en cas de RCIU était initiée à partir de 26 SA. Pour 14% des enfants, il existait une discordance entre la suspicion d’un RCIU en anténatal et un faible poids à la naissance. En cas de discordance, le poids de naissance était le paramètre le plus important pour évaluer le pronostic néonatal. Nos travaux soulèvent des questions sur l’efficacité du dépistage du RCIU en France. Ils montrent la nécessité de développer de nouvelles stratégies de dépistage et de poursuivre les recherches pour mesurer leur impact sur les décisions médicales et sur la santé. / Fetal growth restriction (FGR) is a pregnancy complication that is responsible for significant perinatal mortality and morbidity. Screening for FGR is a key component of prenatal care. The objectives of this thesis were to evaluate the performance of prenatal screening for FGR, to identify the determinants of antenatal suspicion of FGR and to measure its impact on perinatal outcomes. For the first part of the thesis, we used data from the nationally representative French National Perinatal Survey of births (N=14,100 singleton pregnancies): 21.7% of infants with a low birthweight <10th percentile were suspected with FGR during pregnancy and half of infants suspected with FGR had a normal birthweight (false positives). The risk of indicated delivery was higher when FGR was suspected, regardless of the existence of low birthweight, suggesting possible iatrogenic effects. Outcomes were not different for suspected versus unsuspected low birthweight infants. In the second part of the thesis, we used data from the EPIPAGE 2 national cohort of children born before 32 weeks of GA in 2011 (N=3698 singleton non-anomalous infants). Active management for fetal indications in cases of suspected FGR was initiated at 26 weeks. Antenatal and postnatal assessments of FGR were discordant for 14% of infants. When assessments were discordant, birthweight was a better predictor of adverse neonatal outcome. Our results raise questions about the effectiveness of screening strategies for FGR in France. New strategies for the detection of FGR are needed as well as research to measure the impact of screening on medical decisions and health.

Objetivos: identificar los principales factores de riesgo para recién nacidos a término pequeños para edad gestacional (PEG).Materiales y métodos: cohorte retrospectiva que utilizó los datos del Sistema Informático Materno Perinatal del Hospital María Auxiliadora de Lima, Perú, durante el período 2000-2010. Se evaluó la edad materna, la paridad, el nivel educativo, el estado civil, el índice de masa corporal pregestacional, el número de controles prenatales (CPN), la presencia de patologías como preeclampsia, eclampsia, infección urinaria y diabetes gestacional como factores de riesgo para PEG. El peso para la edad gestacional fue calculado en base a percentiles peruanos. Se calculó los riesgos relativos crudos (RR) y ajustados (RRa) con sus respectivos intervalos de confianza al 95% para cada variable con respecto a la condición de PEG usando modelos lineales generalizados log binomial. Resultados: se incluyó a un total de 64 670 gestantes. La incidencia de PEG fue de 7,2%. La preeclampsia (RRa 2,0; IC 95% 1,86-2,15), la eclampsia (RRa 3,22; IC 95% 2,38-4,35), el bajo peso materno (RRa 1,38; IC 95%: 1,23- 1,54), la nuliparidad (RRa 1,32; IC 95%: 1,23-1,42) y la edad ≥35 años (RRa 1,16; IC 95% 1,04- 1,29) se encontraron asociados con un riesgo mayor de recién nacido PEG. Asimismo, un número de 0-2 CPN (RRa 1,43; IC95%: 1,32-1,55), y 3-5 CPN (RRa 1,22; IC 95%: 1,14-1,32) también se encontraron asociados con un riesgo mayor de recién nacido PEG, comparado con 6-8 CPN. Un número de ≥9 CPN (RRa 0,74; IC 95%: 0,69-0,80) fue factor protector. Conclusiones: es necesario identificar a las gestantes con factores de riesgo como los encontrados en este estudio, para disminuir la condición de PEG. Se debe actuar rigurosamente, poniendo especial énfasis en factores modificables, tales como la frecuencia de sus controles prenatales. / Objective: to identify the main risk factors for term infants small for gestational age (SGA). Materials and methods: we conducted a retrospective cohort study using the database of Hospital María Auxiliadora, Lima, Peru, with information of all pregnant women during the period 2000-2010. We analyzed maternal age, parity, educational level, marital status, pre-pregnancy body mass index, number of prenatal visits (PNV), the presence of diseases such as preeclampsia, eclampsia, urinary tract infection and gestational diabetes as risk factors for SGA. The weight for gestational age was calculated on Peruvian percentiles. Crude relative risks (RR) and adjusted relative risk (aRR) with their respective confidence intervals at 95% for each variable was calculated using log binomial generalized linear models. Results: A total of 64 670 pregnant were included. The incidence of SGA was 7.2%. Preeclampsia (aRR 2.0, 95% CI: 1.86 to 2.15), eclampsia (aRR 3.22, 95% CI: 2.38 to 4.35), low maternal weight (aRR 1.38; 95% CI: 1.23 to 1.54), nulliparity (aRR 1.32; 95% CI: 1.23 to 1.42) and age ≥35 years (aRR 1.16, 95% CI: 1.04 to 1.29) were associated with an increased risk for newborn SGA. Also, a number of 0-2 PNV (aRR 1.43, 95% CI: 1.32 to 1.55), and 3-5 PNV (aRR 1.22; 95% CI: 1.14 to 1.32) were also found associated with an increased risk of newborn SGA, compared with 6-8 PNV. A number of ≥9 PNV (aRR 0.74; 95% CI: 0.69 to 0.80) was a protector factor. Conclusions: it is necessary to identify pregnant women with risk factors such as those found in this study, in order to reduce SGA. Particular emphasis on modifiable factors, such as the frequency of antenatal care visits, must be taken. / Tesis

Background: Preeclampsia, small for gestational age (SGA), placental abruption, and fetal death are pregnancy complications linked to the utero-placental vasculature with serious consequences for maternal and infant well-being. Elevated homocysteine, a marker of cardiovascular disease risk, is postulated to play a role in placenta-mediated complications, but epidemiologic studies have reported inconsistent findings. The two primary objectives of this thesis were to 1: comprehensively investigate the association of homocysteine with placenta-mediated complications and examine modifying effects of pre-specified factors on this association, and 2: comprehensively investigate determinants of maternal homocysteine during pregnancy. Methods: A systematic review and meta-analysis of prospective studies was conducted to address thesis objective 1. The Ottawa and Kingston (OaK) Birth Cohort, a prospective cohort study that recruited pregnant women between 2002 and 2009, was used to address thesis objectives 1 and 2. Homocysteine concentration was measured between 12 and 20 weeks gestation. Analyses based on the OaK Birth Cohort consisted of multivariable regressions using restricted cubic splines to model associations with continuously distributed variables. Results: Objective 1: In an analysis of 7587 participants, a significant association between homocysteine concentration and a composite outcome of any placenta-mediated complication was observed (odds ratio (OR) for a 5 µmol/L increase: 1.63, 95% Confidence Interval (CI) 1.23-2.16) and SGA (OR 1.76, 95% CI 1.25-2.46), with potential modifying effects of the methylene tetrahydrofolate reductase (MTHFR) 677C>T variant (SGA) and high-risk pregnancy (preeclampsia). In the systematic review identifying 30 prospective cohort or nested case-control studies, a random effects meta-analysis of pooled mean differences in homocysteine between cases and controls in 28 studies revealed significantly higher means for SGA: 0.35 µmol/L (95% CI 0.19 to 0.51, I2=33%); and preeclampsia: 0.87 µmol/L (95% CI 0.52 to 1.21, I2=92%). Significant sources of heterogeneity were study region (SGA and preeclampsia), adjusting for covariates (preeclampsia), folate status (preeclampsia), and severity (preeclampsia). Objective 2: In 7587 OaK participants, factors related to favourable health status were associated with lower maternal homocysteine concentrations. Folic acid supplementation during pregnancy of >1 mg/day did not substantially increase serum folate concentration. Conclusion: This thesis suggests an independent effect of slightly higher homocysteine concentration in the early to mid-second trimester on the risk of any placenta-mediated complication, SGA, and preeclampsia. Modifying effects explain some of the variability in previous studies. Favourable preconception health status was associated with lower maternal homocysteine.

Kardiopulmonale Adaptation und Therapie von wachstumsretardierten Frühgeborenen mit intrauteriner Perfusionsstörung im Vergleich zu nicht-wachstumsretardierten Frühgeborenen ohne intrauterine Perfusionsstörung Eingereicht von: Christin Lenk, geb. Demolt angefertigt in der Universitätsklinik und Poliklinik für Kinder und Jugendliche in Leipzig, Neonatologische Intensivstation betreut von Frau Prof. Dr. med. Eva Robel-Tillig Juli 2012 Chronische intrauterine Hypoxie bedingt durch uterine, feto-maternale und fetale Perfusionsstörung führt zur fetalen Wachstumsrestriktion und Erhöhung der fetalen und neonatalen Morbidität und Mortalität. Die pränatale Kreislaufzentralisation stellt einen pathophysiologischen Kompensationsmechanismus dar, der durch Umverteilung des Blutflusses eine Versorgung lebenswichtiger Organe des Feten sichert (Rizzo et al. 2008), (Robel-Tillig 2003), (Robel 1994), (Saling 1966). In den letzten Jahren haben sich Studien mit der postnatalen Adaptation der wachstumsretardierten Neonaten beschäftigt und wesentliche Risiken im Verlauf der ersten Lebenstage definiert. Wenige validierte Aussagen existieren jedoch zur Kreislaufsituation der betroffenen Kinder und der kardialen Leistungsfähigkeit auch über die erste Lebenswoche hinaus. Die vorliegende Studie vergleicht unter dieser Fragestellung eine Gruppe von 43 Frühgeborenen mit intrauteriner Wachstumsrestriktion auf der Grundlage einer Perfusionsstörung und 33 Frühgeborene mit appropriatem Wachstum und ungestörter pränataler Perfusion während der ersten 42 Lebenstage hinsichtlich der unmittelbaren postnatalen pulmonalen und kardialen Adaptationsparameter und des weiteren klinischen Verlaufs. Besonderer Schwerpunkt wird dabei auf die dopplersonographisch erfasste kardiale Funktion der Kinder gelegt. Als wesentlichstes Ergebnis der dopplersonographischen Messungen lässt sich bei den Frühgeborenen mit pränataler Perfusionsstörung ein signifikant erhöhtes Herzminutenvolumen rechts- und linksventrikulär im Vergleich zur Gruppe der Frühgeborenen mit ungestörter Perfusion darstellen (Robel-Tillig 2003), (Leipälä et al. 2003), Martinussen 1997}, (Guajardo, Mandelbaum & Linderkamp 1994), (Lindner et al. 1990). Die unmittelbar postnatale Adaptation zeigt hinsichtlich des arteriellen Nabelschnur-pH-Wertes eine schlechtere Anpassung der Frühgeborenen mit pränataler Perfusionsstörung auf. Im weiteren Verlauf der ersten Tage benötigen diese Frühgeborenen seltener eine maschinelle Beatmung oder CPAP-Atemhilfe als die Frühgeborenen ohne Wachstumsrestriktion. Bis zum 42. Lebenstag kehrt sich dieser Befund jedoch um. Die Frühgeborenen mit Wachstumsrestriktion bedürfen nun signifikant länger und häufiger einer Atemhilfe und zusätzlicher Sauerstoffsupplementierung. Als Komplikation trat bei den wachstumsretardierten Frühgeborenen eine höhere Rate an bronchopulmonaler Dysplasie auf. Ein weiterer Unterschied wird hinsichtlich der Transfusionshäufigkeit dargestellt. Frühgeborene mit Wachstumsrestriktion erhielten häufiger eine Erythrozytentransfusion und länger eine Transfusion von zusätzlichem Volumen. Zusammenfassend weisen die ermittelten Befunde auf ein Persistieren der intrauterin bestehenden Kompensation der beeinträchtigten Kreislaufsituation hin. Eine genaue Kenntnis der speziellen Probleme dieser Patientengruppe ist zur Vermeidung postnatal anhaltender hämodynamischer Störungen erforderlich.

Background: The prevalence of opioid use disorder has increased across the United States, but the rural population of Appalachia has been disproportionately impacted. Concurrently, the slow, but steady progress in the legalization of marijuana may be affecting perception of marijuana use in pregnancy. However, marijuana use in pregnancy has been associated with adverse perinatal outcomes. Concomitant use of opioids and marijuana in pregnancy has not been evaluated. Objective: The primary aim of the study was to evaluate the association between confirmed marijuana use in late pregnancy and preterm birth in opioid-exposed pregnancies. Methodology: A retrospective chart review was conducted that included all births from July 2011 to June 2016 from 6 delivery hospitals in South-Central Appalachia. Out of 18,732 births, 2368 singleton pregnancies indicated opioid use and met remaining inclusion criteria, with 108 of these mothers testing positive for marijuana at delivery. Independent sample t-test and Chi-Square analyses compared marijuana and non-marijuana exposed groups on maternal and neonatal outcomes. Regression analyses controlled for confounding variables in predicting neonatal abstinence syndrome (NAS), NICU admission, preterm birth, small for gestational age, and low birth weight outcomes as shown in Table 1. Results: Neonates born to marijuana-positive women in opioid-exposed pregnancy were more likely to be born preterm, small for gestational age, have low birth weight, and be admitted to NICU. After statistically controlling for parity, marital status, tobacco and benzodiazepine use, preterm birth and low birth weight remained statistically significant with aOR of 2.35 (1.30–4.24) and 2.01 (1.18–3.44), respectively. Conclusions: Maternal use of marijuana in any opioid-exposed pregnancy may increase risk of preterm birth and low-birth weight infants. Prospective studies need to examine the dose and timing of marijuana and opioid use in pregnancy to better delineate perinatal effects. Nonetheless, pregnant women using opioids, including recommended medication assisted treatment for opioid use disorder, should be educated about the risks of concurrent marijuana use during pregnancy and may need to be counseled to abstain from marijuana use during pregnancy for an optimal outcome.

No description available.

This study has determined the cellular site of adenosine deaminase (ADA) expression in the mouse during development from Days 5 through 13 (day vaginal plug was found = Day 0) of gestation. Developmental expression of ADA progressed in two overlapping phases defined genetically (maternal vs. embryonal) and according to region (decidual vs. placental). In the first phase, ADA enzyme activity increased almost 200-fold in the antimesometrial region (decidua capsularis + giant trophoblast cells) from Days 6 through 9 of gestation but remained low in the mesometrial region. Immunohistochemical staining revealed a major localization of ADA to the secondary decidua. In the second phase, ADA activity increased several-fold in the placenta (labyrinth + basal zones) from Days 9 through 13 of gestation but remained low in the embryo proper. Immunohistochemical staining revealed a major localization of ADA to secondary giant cells, spongiotrophoblast, and labyrinthine trophoblast. Regression of decidua capsularis and growth of the spongiotrophoblast population accounted for an antimesometrial to placental shift in both ADA enzyme activity and a 40-kDa immunoreactive protein band. To verify a shift from maternal to fetal expression, studies were performed with two strains of mice (ICR, Eday) homozygous for a different ADA isozyme (ADA-A, ADA-B). Blastocysts homozygous for Adab were transferred to the uterus of pseudopregnant female recipients homozygous for Adaa. The isozymic pattern in chimeric embryo-decidual units analyzed at Days 7, 9, 11, and 13 revealed a predominance of maternal-encoded enzyme at Days 7 through 11 of gestation and a shift to fetal-encoded enzyme by Day 13. Thus, maternal expression of ADA in the antimesometrial decidua may play a role during establishment of the embryo in the uterine environment, whereas fetal expression of ADA in the trophoblast might be important to placentation.

The type and duration of observation and monitoring of mother and fetus after abdominal trauma are dependent on gestational age and severity of trauma. Fetal monitoring is usually not required when the fetus is not viable; the primary consideration is the safety of the mother. When the fetus is viable, 24-hour inpatient fetal monitoring is indicated in cases of major trauma, even when no symptoms of injury are obvious.

In current resuscitation guidelines, tactile stimulation is recommended for infants with insufficient respiratory efforts after birth. No recommendations are made regarding duration, onset, and method of stimulation. Neither is mentioned how tactile stimulation should be applied in relation to the gestational age. The aim was to review the physiological mechanisms of respiratory drive after birth and to identify and structure the current evidence on tactile stimulation during neonatal resuscitation. A systematic review of available data was performed using PubMed, covering the literature up to April 2021. Two independent investigators screened the extracted references and assessed their methodological quality. Six studies were included. Tactile stimulation management, including the onset of stimulation, overall duration, and methods as well as the effect on vital parameters was analyzed and systematically presented. Tactile stimulation varies widely between, as well as within different centers and no consensus exists which stimulation method is most effective. Some evidence shows that repetitive stimulation within the first minutes of resuscitation improves oxygenation. Further studies are warranted to optimize strategies to support spontaneous breathing after birth, assessing the effect of stimulating various body parts respectively within different gestational age groups.