Marije Hogeveen

Maternal homocysteine and small-for-gestational-age offspring: systematic review and meta-analysis

BACKGROUNDnGrowth retardation in utero leading to small-for-gestational-age (SGA) newborns is associated with increased neonatal morbidity and mortality and with lifelong consequences such as poor cognitive function and cardiovascular diseases. Maternal total homocysteine (tHcy) concentrations have been linked to a wide range of adverse pregnancy outcomes and could possibly influence birth weight.nnnOBJECTIVEnWe performed a systematic review of and meta-analysis on the association of maternal tHcy and birth weight.nnnDESIGNnA literature search of English, German, and French publications with the use of the PubMed database (January 1966-July 2010) found 78 abstracts. Search terms were as follows: homocysteine AND (birth weight OR small for gestational age OR intrauterine growth retardation). Studies were eligible if information on maternal tHcy and birth weight and the possible association between maternal tHcy and birth weight was available. Effect size estimates were converted to ORs as estimates of the RR of a woman to deliver SGA offspring when maternal tHcy exceeded the 90th percentile.nnnRESULTSnThe search yielded 19 studies for analysis, consisting of 21,326 individuals. Pooled analysis resulted in a crude OR of 1.25 (95% CI: 1.09, 1.44). When this estimate was expressed as a linear effect, it corresponded to a decrease in birth weight of 31 g (95% CI: -13, -51 g) for a 1-SD increase in maternal tHcy.nnnCONCLUSIONSnHigher maternal tHcy concentrations are associated with a small increased risk for SGA offspring. The small estimated birth weight difference might be of little clinical relevance for the individual newborn; however, it could be of greater importance at a population level.

Maternal homocysteine and related B vitamins as risk factors for low birthweight

OBJECTIVEnWe designed a large prospective study to explore the relationship between maternal homocysteine concentrations and related B vitamins and birthweight.nnnSTUDY DESIGNnBlood was sampled from pregnant women at 30-34 weeks of gestation and their newborn infants (n = 366).nnnRESULTSnConcentrations of all analytes were higher in umbilical cord compared with maternal samples. Birthweight was related negatively to maternal homocysteine (r = -0.12) but not related to maternal cobalamin, methylmalonic acid, and folate (r = 0.02, r = 0.06, and r = 0.04, respectively). Regression analysis revealed smoking (beta = -313; 95% confidence interval [CI], -479 to -149), gestational age (beta = 150; 95% CI, 118-182), female sex (beta = -146; 95% CI, -256 to -35), and parity (beta = 104; 95% CI, 37-171) as strong determinants of birthweight. Maternal homocysteine, cobalamin, methylmalonic acid, and folate were not determinants of birthweight in multivariate analysis.nnnCONCLUSIONnMaternal homocysteine and B vitamins are not related to birthweight in a multivariate model that was adjusted for potential confounders.

Umbilical choline and related methylamines betaine and dimethylglycine in relation to birth weight

Background:Low birth weight (LBW) is associated with increased morbidity and mortality for the newborn and risk of chronic disease in adulthood. Choline plays an essential role in the integrity of cell membranes, methylation reactions, and memory development. We examined whether choline, betaine, and dimethylglycine (DMG) concentrations were associated with LBW in Dutch women.Methods:Blood was sampled from umbilical cords (UCs) at delivery in singleton pregnancies (n = 1,126). Maternal blood was sampled at 30–34u2009wk of gestational age (GA) (n = 366). We calculated birth weights standardized for GA and defined LBW as standardized birth weight ≤2,500u2009g.Results:Maternal concentrations were lower as compared with UC concentrations and were not associated with birth weight. UC choline and betaine were inversely associated with birth weight (β = −60 (−89, −31) and β = −65 (−94, −36), respectively), whereas UC DMG was positively associated with birth weight (β = 35 (6.1, 63)). Odds ratios for LBW were 4.12 (1.15, 14.78), 5.68 (1.24, 25.91), and 0.48 (0.09, 2.65) for the highest UC choline, betaine, and DMG quartiles, respectively, as compared with the lowest quartiles.Conclusion:We observed an increased risk of LBW with increased umbilical choline and betaine in venous UC blood. These results might reflect a change in choline consumption or metabolism or a disturbed placental function.

Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analysis of Individual Participant Data

Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500xa0g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148xa0pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio =xa01.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratioxa0=xa01.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

Using simulation to study difficult clinical issues: prenatal counseling at the threshold of viability across american and dutch cultures

Objective Prenatal counseling at the threshold of viability is a challenging yet critically important activity, and care guidelines differ across cultures. Studying how this task is performed in the actual clinical environment is extremely difficult. In this pilot study, we used simulation as a methodology with 2 aims as follows: first, to explore the use of simulation incorporating a standardized pregnant patient as an investigative methodology and, second, to determine similarities and differences in content and style of prenatal counseling between American and Dutch neonatologists. Methods We compared counseling practice between 11 American and 11 Dutch neonatologists, using a simulation-based investigative methodology. All subjects performed prenatal counseling with a simulated pregnant patient carrying a fetus at the limits of viability. The following elements of scenario design were standardized across all scenarios: layout of the physical environment, details of the maternal and fetal histories, questions and responses of the standardized pregnant patient, and the time allowed for consultation. Results American subjects typically presented several treatment options without bias, whereas Dutch subjects were more likely to explicitly advise a specific course of treatment (emphasis on partial life support). American subjects offered comfort care more frequently than the Dutch subjects and also discussed options for maximal life support more often than their Dutch colleagues. Conclusions Simulation is a useful research methodology for studying activities difficult to assess in the actual clinical environment such as prenatal counseling at the limits of viability. Dutch subjects were more directive in their approach than their American counterparts, offering fewer options for care and advocating for less invasive interventions. American subjects were more likely to offer a wider range of therapeutic options without providing a recommendation for any specific option.

The effect of folinic acid supplementation on homocysteine concentrations in newborns.

Objective:The incidence of cerebrovascular accidents (CVA) occurring perinatally is relatively high and aspects of the multifactorial pathophysiology remain unclear. Elevated homocysteine concentrations have been shown to be associated with an increased risk for CVA in children and even in newborns. We studied the possible homocysteine lowering effect of folinic acid in newborns.Method:We included 37 newborns in our prospective randomized folinic acid (given as 5-formyltetrahydrofolate) intervention study from patients admitted to our neonatal intensive care unit (18 controls, 19 intervention group). We measured total homocysteine (tHcy) and plasma folate concentrations at three time points (baseline, 1 and 2 weeks after intervention). The intervention group was treated with folinic acid (70u2009μg/kg/day) for 2 weeks. We calculated median concentrations (25th and 75th percentiles).Results:Median tHcy concentrations at the three time points did not differ from each other in the control group nor in the intervention group. We also could not observe different tHcy concentrations between both groups. Plasma folate concentrations increased in the intervention group (mean increase 167% (95% confidence interval (CI) −291, 625)) compared with control group (mean increase −12% (95% CI −132, 108)), P for treatment effect: 0.03.Conclusion:We could not demonstrate a homocysteine lowering effect of folinic acid administration in newborns. This indicates that one carbon metabolism in newborns differs form adults. Cobalamin might be a better strategy to lower tHcy concentrations in newborns.

Prenatal (non)treatment decisions in extreme prematurity: evaluation of Decisional Conflict and Regret among parents

Objective:To evaluate Decisional Conflict and Regret among parents regarding the decision on initiating comfort or active care in extreme prematurity and to relate these to decision-making characteristics.Study Design:A nationwide, multicenter, cross-sectional study using an online survey in the Netherlands. Data were collected from March 2015 to March 2016 among all parents with infants born at 24+0/7–24+6/7 weeks gestational age in 2010–2013. The survey contained a Decisional Conflict and Decision Regret Scale (potential scores range from 0 to 100) and decision-making characteristics.Results:Sixty-one surveys were returned (response rate 27%). The median Decisional Conflict score was 28. From the subscores within Decisional Conflict, ‘values clarity’ revealed the highest median score of 42—revealing that parents felt unclear about personal values for benefits and risks of the decision on either comfort care or active care. The median Decision Regret score was 0. Regret scores were influenced by the actual decision made and by outcome: Decision Regret was lower in the active care group and in the survivor group.Conclusion:We found little Decisional Conflict and no Decision Regret among parents regarding decision-making at 24 weeks gestation.

Various experiences and preferences of Dutch parents in prenatal counseling in extreme prematurity

OBJECTIVEnTo investigate experienced and preferred prenatal counseling among parents of extremely premature babies.nnnMETHODSnA Dutch nationwide, multicenter, cross-sectional study using an online survey. Surveys were sent to all parents of extremely premature babies born between 2010 and 2013 at 24+0/7-24+6/7 weeks of gestation.nnnRESULTSnSixty-one out of 229 surveys were returned. A minority (14%) had no counseling conversation. Conversations were done more often by neonatologists (90%) than by obstetricians (39%) and in 37% by both these experts. Supportive material was rarely used (19%). Mortality (92%) and short-term morbidity (88%) were discussed the most, and more frequently than long-term morbidity (65%), practical items (63%) and delivery mode (52%). Most decisions on active care or palliative comfort care were perceived as decisions by doctor and parents together (61%). 80% felt they were involved in decision-making. The preferred way of involvement in decision-making varied among parents.nnnCONCLUSIONnThe vast majority of parents were counseled: mostly by neonatologists, and mainly about mortality and short-term morbidity. Parents wanted to be involved in the decision-making process but differed on the preferred extent of involvement. Practice implications Understanding of shared decision-making may contribute to meet the various preferences of parents.

Maternal Homocysteine in Association with Birth Weight: Systematic Review and Meta-Analysis

Background and aims: Low birth weight (LBW), as a proxy for fetal growth, is associated with increased neonatal morbidity and mortality but also with life-long consequences such as poor cognitive function and cardiovascular diseases. Maternal total homocysteine concentrations (tHcy) have been linked to a wide range of adverse pregnancy outcomes and could possibly influence birth weight. We performed a systematic review and meta-analysis on the association of maternal tHcy and birth weight.Methods: An electronic literature search revealed 78 abstracts. Studies were eligible if information on maternal tHcy, birth weight and the possible association between maternal tHcy and birth weight was available. Effect estimates were converted to odds ratios with a cut-off level of birth weight < 10th percentile for gestational age (SGA) and maternal tHcy >90th percentile.Results: The search yielded 19 studies for analysis, consisting of 21,326 individuals. Pooled analysis resulted in a crude OR of 1.30[1.14;1.49] (relative risk to get an infant born SGA when maternal tHcy is>90th percentile). This estimate corresponds to -43[-19;-56] g for 1sd increase in maternal tHcy. Adjustment for known confounders was not possible but a tendency to decreased strength of association was observed in studies after adjustment for strong determinants.Conclusion: Higher maternal tHcy concentrations are associated with increased risk for being born SGA. Adjustment for possible confounders was performed in some but not all studies. The small estimated birth weight difference might be of little clinical relevance for the individual newborn, however, it could be of greater importance on population level.

Simulatieteamtraining in de spoedeisende kindergeneeskunde

SamenvattingDe opvang van het ernstig zieke kind of de bedreigde pasgeborene stelt hoge eisen aan de individuele kinderarts en zijn/haar teamleden. Dit heeft geleid tot de ontwikkeling van een aantal kindergeneeskundige advanced life support-cursussen. Het accent ligt hierbij op het verwerven en integreren van kennis en vaardigheden. Er wordt echter niet of nauwelijks ingegaan op het functioneren van de diverse betrokkenen in een team. Simulatieteamtraining lijkt een goede methode om de diverse competenties noodzakelijk voor een optimale teamprestatie te trainen. In een andere ruimte (de debriefing-ruimte) kunnen andere professionals de simulatie via een beeldscherm volgen. Na afloop vindt een uitgebreide (team)feedback plaats aan de hand van de opgenomen videobeelden. Deze debriefing is essentieel voor het leereffect.SummaryTimely and appropriate paediatric emergency care is required for the functional survival of critically ill children and neonates. For this reason a number of advanced life support courses has been developed training task work skills, which includes lectures, skill stations and interactive sessions that integrate knowledge and skills. However, the skills that team members need to function effectively as part of a team are often not trained. Simulation team training offers a method to train the skills needed to turn a team of experts into an expert medical team. The simulation is recorded and the recording is used to inform the debriefing. This is essential for the educational efficacy.