Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace

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Doppler investigation of placental blood flow in the second trimester: a screening study for pre-eclampsia and growth retardation

In a cross-sectional study of 977 women recruited from the booking ultrasound clinic at 16-24 weeks gestation, the resistance index (RI) in the uteroplacental circulation and umbilical artery were measured by continuous wave Doppler ultrasound. Reference ranges for these indices were constructed and their relation to maternal social factors and morphometry established. Pregnancies with high values had a higher incidence of pre-eclampsia, abruptio, small-for-gestational age babies, and fetal wastage. Cut-off levels for sensitivity and specificity for the prediction of complications were produced. Additional studies were made. The RI varied with uterine site and placental location so a new methodology for insonation was developed. Confirmation of the vessel studied was supplied by colour flow mapping and in-vivo studies at laparotomy. The intra-observer error was established. The feasibility of the screening study and methodology were tested in a pilot study of 21 women. The hospital computer provided pregnancy and delivery details in 832 cases. The reliability of the data was assessed in a comparative study of 50 cases. In the remaining 145 cases information was collected after a series of searches including 2 postal requests to GPs and subjects. Follow-up was successful in 96.5% of cases. In 237 cases where pregnancy complications were recorded the medical notes were retrieved and 3 independent observers coded the diagnoses. The changes in RI with gestation observed in the cross-sectional study were confirmed in a longitudinal study of 33 women from 16-40 weeks. A postpartum study of 21 women suggested the restitution of the uteroplacental circulation to its non-pregnant state does not occur immediately after delivery. Predictions of pregnancy complications by Doppler parameters were compared to one another and to an obstetric risk score. Furthermore, in 183 women, the maternal serum AFP, HPL, BHCG, PAPP-A, SPl and PP12 were poorer predictors than Doppler ultrasound

Volumetric Blood Flow and Assessment of the Metabolic Profile of the Developing Brain in Growth Restricted Fetuses: An Ultrasound and Proton Magnetic Resonance Spectroscopy Study

Introduction Intrauterine growth restriction (IUGR) is a common obstetric condition causing significant perinatal morbidity and mortality. A phenomenon known as brain sparing occurs in IUGR fetuses whereby blood is preferentially diverted to supply the developing brain often at the expense of other organs. However, although this supposedly neuroprotective mechanism exists, children that were growth restricted in utero have a higher incidence of long term neurodevelopmental sequelae. This thesis therefore aims to explore the brain redistribution phenomenon in detail by investigating cerebral volume blood flow and the metabolic profile of the IUGR brain using high resolution ultrasound and proton magnetic resonance spectroscopy respectively. Methods 150 appropriately grown and 78 IUGR fetuses had volume blood flow assessed longitudinally using high resolution ultrasound and power Doppler in multiple fetal vessels. The metabolic status of the brain was then assessed in 46 appropriately grown and 26 growth restricted fetuses using Proton Magnetic Resonance Spectroscopy. Results IUGR fetuses had a generalised increase in vessel diameter in comparison with appropriately grown control fetuses, and when standardised for weight, increased volume blood flow was noted in the middle cerebral, renal, umbilical and carotid arteries and the ascending aorta. No difference in flow was noted in the descending aorta. N-acetylaspartate:Choline and N-acetylaspartate:Creatine ratios were reduced in IUGR fetuses and lactate was present in the developing brains of both appropriately grown and growth restricted fetuses. Conclusions Volume blood flow is significantly altered in IUGR fetuses, likely to be mediated by alterations in vessel diameter. This may be secondary to alterations in circulating vasoactive factors or as a result in alterations of the composition of vessel walls. The metabolic status of the brain tissue is also altered which may in part explain the higher incidence of neurodevelopmental sequelae in some fetuses that were growth restricted in utero

Metformin, metabolomics and inflammation in gestational diabetes

Gestational diabetes is a common pregnancy complication that increases the risk of adverse pregnancy outcomes and predicts long-term metabolic morbidity for the mother and the offspring. Gestational diabetes is treated with lifestyle modifications and metformin or insulin if needed. Besides hyperglycemia, gestational diabetes is associated with broad disturbances in lipid and amino acid metabolism and lowgrade inflammation. The effects of metformin on these changes compared to insulin are not fully known. In this secondary analysis of a previous randomized trial in gestational diabetes, the effects of metformin (n = 110) and insulin (n = 107) treatments were studied on the maternal metabolome, inflammatory marker profile and insulin-like growth factor-binding protein-1 phosphoisoforms. Patients (n = 126) not requiring antihyperglycemic medication were included as a reference group at the time of randomization to medical treatment groups. Umbilical cord blood samples were drawn after delivery in all three groups to study the effects of metformin on the fetal metabolome. Metformin treatment led to a greater increase in maternal serum alanine, total triglycerides, very low-density lipoprotein triglycerides and total fatty acids than insulin. In the cord serum metabolome, only alanine was significantly higher in the metformin group. Maternal lipids, very low-density lipoprotein cholesterol and the apolipoprotein B to A-1 ratio in particular, were related to an increased birth weight and these associations were stronger in the metformin group than the insulin group. In cord blood, omega-6 fatty acids were positively and omega-3 fatty acids inversely associated with birth weight. Metformin had no effects on fetal ketones or fetal lipid metabolism. In conclusion, insulin treatment of gestational diabetes may be more effective than metformin in ameliorating maternal dyslipidemia, although birth weight and other pregnancy outcomes were similar among the study groups. Our results suggest that the maternal metabolome could be helpful in identifying patients who benefit the most from metformin or insulin treatment. The long-term implications of elevated cord serum alanine merits further study.Metformiini, metabolomiikka ja inflammaatio raskausdiabeteksessa Raskausdiabetes on yleinen ongelma, joka lisää raskauden riskejä sekä ennustaa äidin ja lapsen myöhempää sairastavuutta. Raskausdiabetesta hoidetaan elintapamuutoksin sekä tarvittaessa lääkehoidolla. Korkean verensokerin lisäksi raskausdiabetekseen liittyy rasva- ja aminohappoaineenvaihdunnan sekä matalaasteisen tulehduksen häiriöitä. Toistaiseksi metformiinin vaikutuksia näihin muutoksiin insuliinihoitoon verrattuna ei kunnolla tunneta. Tässä aiemman satunnaistetun tutkimuksen jatkoanalyysissa verrattiin raskausdiabeteksen metformiini- (n = 110) ja insuliinihoitojen (n = 107) vaikutuksia äidin aineenvaihdunnan molekyyleihin (metabolomiin), tulehdusmerkkiaineisiin ja insuliinin kaltaista kasvutekijää sitovaan proteiini 1:een. Lääkehoidon aloitusvaiheen vertailuun otetiin myös potilaita (n = 126), jotka eivät tarvinneet verenglukoosia alentavaa lääkitystä. Napanuoraverinäytteet otettiin synnytyksen jälkeen kaikissa kolmessa ryhmässä metformiinin vaikutusten tutkimiseksi. Metformiinihoidetuilla äideillä seerumin alaniinin, triglyseridien kokonaismäärän, erittäin matalatiheyksisten lipoproteiinien triglyseridien sekä rasvahappojen kokonaismäärän pitoisuudet nousivat enemmän kuin insuliinihoidetuilla. Napaveren metabolomissa ainoastaan alaniini oli merkitsevästi korkeampi metformiiniryhmässä. Äidin verenkierrossa erityisesti erittäin matalatiheyksisen lipoproteiinin kolesteroli sekä apolipoproteiini B:n ja A-1:n suhde olivat yhteydessä korkeampaan syntymäpainoon ja nämä yhteydet olivat vahvempia metformiiniryhmässä. Napaveressä omega-6-rasvahapot liittyivät korkeampaan ja omega-3-rasvahapot matalampaan syntymäpainoon. Metformiinilla ei ollut vaikutuksia sikiön ketoneihin tai rasva-aineenvaihduntaan. Raskausdiabeteksen insuliinihoito metformiiniin verrattuna saattaa olla tehokkaampi äidin rasva-aineenvaihdunnan muutosten lieventämisessä, vaikka syntymäpainoissa tai raskauskomplikaatioissa ei ollut eroja ryhmien välillä. Tulokset viittaavat siihen, että tulevaisuudessa äidin metabolomista voisi olla apua niiden potilaiden tunnistamisessa, jotka hyötyvät ensisijaisesti joko metformiini- tai insuliinihoidosta. Kohonneen napaveren alaniinin mahdolliset vaikutukset lasten myöhempään terveyteen vaativat lisätutkimuksia