Role of PFKFB3-driven glycolysis in vessel sprouting.

Vessel sprouting by migrating tip and proliferating stalk endothelial cells (ECs) is controlled by genetic signals (such as Notch), but it is unknown whether metabolism also regulates this process. Here, we show that ECs relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation. Mechanistically, PFKFB3 not only regulated EC proliferation but also controlled the formation of filopodia/lamellipodia and directional migration, in part by compartmentalizing with F-actin in motile protrusions. Mosaic in vitro and in vivo sprouting assays further revealed that PFKFB3 overexpression overruled the pro-stalk activity of Notch, whereas PFKFB3 deficiency impaired tip cell formation upon Notch blockade, implying that glycolysis regulates vessel branching.

Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn.

BACKGROUND: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels. METHODS: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%). RESULTS: Live birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity. CONCLUSIONS: Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.).

Establishing correlates of maternal-fetal cytomegalovirus transmission-one step closer through predictive modeling.

BACKGROUND: Determinants of maternal-fetal cytomegalovirus (CMV) transmission and factors influencing the severity of congenital CMV (cCMV) infection are not well understood. METHODS: We conducted a descriptive, multi-center study in pregnant women ≥18 years old with primary CMV infection and their newborns (NCT01251744) to explore maternal immune responses to CMV and determine potential immunologic/virologic correlates of cCMV following primary infection during pregnancy. We developed alternative approaches looking into univariate/multivariate factors associated with cCMV, including a participant clustering/stratification approach and an interpretable predictive model-based approach using trained decision trees for risk prediction (post-hoc analyses). RESULTS: Pregnant women were grouped in three distinct clusters with similar baseline characteristics, particularly gestational age at diagnosis. We observed a trend for higher viral loads in urine and saliva samples from mothers of infants with cCMV versus without cCMV. When using a trained predictive-model approach that accounts for interaction effects between variables, anti-pentamer IgG antibody concentration and viral load in saliva were identified as biomarkers jointly associated with the risk of maternal-fetal CMV transmission. CONCLUSION: We identified biomarkers of CMV maternal-fetal transmission. After validation in larger studies, our findings will guide the management of primary infection during pregnancy and the development of vaccines against cCMV.

The human cytomegalovirus (CMV) is common and usually causes no symptoms in healthy individuals. However, CMV infections can be life-threatening in individuals with improperly functioning or immature immune systems, such as fetuses. Women can become infected with CMV for the first time (primary infection) during pregnancy. If CMV is transmitted from mother to fetus before the second trimester, the infant can suffer from severe disorders such as hearing loss and delayed development. We aimed to identify characteristics of pregnant women with a primary CMV infection that may increase the likelihood of transmitting CMV to the fetus. We considered demographical, clinical, and behavioral characteristics, as well as immune responses and the quantity of virus detected in the women's blood, urine, saliva, and vaginal mucus. Because we could not identify one single characteristic that could predict a high risk of CMV transmission, we developed new data analysis models to study how they can be combined. We found that antibodies targeting a pentameric antigen of the virus envelope and the presence of virus in saliva can together predict the risk of CMV transmission from mother to fetus. Our results can help improve the care of CMV-infected pregnant women and the design of CMV vaccines.

Interpregnancy maternal weight change is not associated with offspring weight and obesity at age 2 years.

BACKGROUND: Weight retention between pregnancies is associated with increased risk of perinatal complications, but it is unclear whether there is an association with offspring weight status. This study aimed to determine whether maternal interpregnancy weight change is associated with offspring overweight/obesity, controlling for confounding variables. SUBJECTS/METHODS: Routinely collected linked data from perinatal and child datasets, in Flanders, Belgium were used. Women having their first and second live births between 2009-2018 were included. The association between maternal interpregnancy weight change and overweight/obesity in the second child at 2 years was examined by logistical regression models. RESULTS: A total of 33,172 women were included. 52.7% (n = 17478) had a stable interpregnancy BMI, 24.1% (n = 8024) and 8.5% (n = 2821) had moderate and substantial BMI increases respectively. At 2 years, 91.6% (n = 30383) of the second offspring had a healthy weight, 0.6% (n = 210), 7.0% (n = 2312) and 0.8% (n = 267) were in the underweight, overweight and obesity BMI categories respectively. Multivariate analysis showed no statistical evidence that maternal interpregnancy BMI change is independently associated with overweight/obesity in the second child. The strongest independent factors were the first child (sibling) being in the obesity category at 2 years (odds ratio [OR] 7.2, [95% CI, 5.49-9.45] and being born Large for Gestational Age (LGA) (2.13 [1.92-2.37]). The following variables were also independently associated with the outcome measure: maternal African origin (1.90 [1.59-2.26]), maternal obesity at start of first pregnancy (1.33 [1.16-1.53]), excessive gestational weight gain in the second pregnancy (1.15 [1.04-1.28]), being born after a < 1-year interpregnancy time interval (1.17 [1.05-1.30]) and not being exclusively breastfed at 12 weeks old (1.29 [1.10-1.52]). CONCLUSION: Sibling obesity and being born LGA were most strongly independently associated with overweight/obesity at 2 years. This supports the need for family interventions and to address risk factors for development of LGA infants. There was no independent association with interpregnancy weight gain, contrary to what was hypothesised.

Exteriorization of the uterus reduces fetoscopic cannula-induced stress and strain: A finite element model analysis.

OBJECTIVE: To estimate stresses and strains in the uterine wall and fetal membranes with single/multi-port fetoscopy, simulating either a percutaneous access or via exteriorized uterus. STUDY DESIGN: Finite element models based on anatomical dimensions, material properties and boundary conditions were created to simulate stresses, strains and displacements on the uterine wall and fetal membranes during simulated fetal surgery either via exteriorized uterus or percutaneous approach, and with one or three cannulas. Clinically, we measured the anatomical layer thickness and cannula entry point displacement in patients undergoing single port percutaneous fetoscopy. RESULTS: Simulations demonstrate that single port percutaneous fetoscopy increases stress on the fetal membranes (+105%, 128 to 262 kPa) and uterine wall (+115%, 0.89 to 1.9 kPa) compared to exteriorized uterine access. Using three ports increases stress by 110% (148 to 312 kPa) on membranes and 113% (1.08 to 2.3 kPa) on uterine wall. Finite Element Method showed 0.75 cm uterine entry point displacement from the cutaneous entry, while clinical measurements demonstrated displacement of more than double (1.69 ± 0.58 cm), suggesting modeled measurements may be underestimations. CONCLUSION: The stresses and strains on the fetal membranes and uterus are double as high when entering percutaneously than via an exteriorized uterus. Based on what can be clinically measured, this may be an underestimation.

Length of hysterotomy for fetal spina bifida repair is associated with prematurity risk.

OBJECTIVE: To investigate whether prenatal repair of spina bifida aperta through mini-hysterotomy results in less prematurity, as compared to standard hysterotomy, when adjusting for known prematurity risks. METHODS: We performed a bi-centric, propensity score matched, controlled study, that is, adjusting for factors earlier reported to result in premature delivery or membrane rupture, in consecutive women having prenatal repair either through stapled hysterotomy or sutured mini-hysterotomy (≤3.5 cm). Matches were pairwise compared and cox-regression analysis was performed to define the hazard ratio of delivery <37 weeks. RESULTS: Of 346 meeting the MOMS-criteria, 78 comparable pairs were available for matched-controlled analysis. Mini-hysterotomy patients were younger and had a higher BMI. Mini-hysterotomy was associated with a 1.67-lower risk of delivery <37 weeks (hazard ratio: 0.60; 95% CI: 0.42-0.85; p = 0.004) and 1.72 for delivery <34 + 6 weeks (hazard ratio: 0.58; 95% CI: 0.34-0.97; p = 0.037). The rate of intact uterine scar at birth (mini-hysterotomy: 98.7% vs. hysterotomy: 90.4%; p = 0.070), the rate of reversal of hindbrain herniation within 1 week after surgery (88.9% vs. 97.4%; p = 0.180) and the rate of cerebrospinal fluid leakage (0% vs. 2.7%; p = 0.50) were comparable. CONCLUSION: Prenatal spina bidifa repair through mini-hysterotomy was associated with a later gestational age at delivery and a comparable intact uterus rate without apparent compromise in neuroprotection.

Urogenital cultures and preterm birth in women with cervical cerclage: a single center retrospective cohort study.

BACKGROUND: The leading hypothesis of the pathogenesis of cervical insufficiency suggests a role of cervical inflammation. Urogenital tract infections could play a causative role in this process. To test this hypothesis in women with a cervical cerclage, we aimed to retrospectively examine the relationship between gestational age (GA) at delivery and positive urogenital cultures. METHODS: This single center retrospective study reviewed the records of all women with a singleton pregnancy that underwent cervical cerclage (n = 203) between 2010 and 2020 at the University Hospital of Leuven, Belgium. Transvaginal cerclages were categorized as history indicated (TVC I, n = 94), ultrasound indicated (TVC II, n = 79) and clinically indicated (TVC III, n = 20). Additionally, ten women received transabdominal cerclage (TAC). Urogenital cultures (vaginal and urine) were taken before and after cerclage with 4-week intervals. Urogenital cultures were reported 'positive' if urine and/or vaginal cultures showed significant growth of a microorganism. Treatment decision depended on culture growth and clinical presentation. The primary aim was to evaluate the association between the urogenital culture results and the GA at delivery, for each of the cerclage groups. Secondarily, to investigate the effect of antibiotic treatment of positive cultures on GA at delivery. RESULTS: Positive pre-cerclage urogenital cultures were associated with lower GA at delivery in TVC III (positive culture 26w4d ± 40d vs. negative 29w6d ± 54d, p = 0.036). For TVC I, GA at delivery was longer when pre-cerclage urogenital cultures were positive (positive culture 38w0d ± 26d vs. negative 35w4d ± 42d, p = 0.035). Overall post-cerclage urogenital cultures status was not associated with a different GA at delivery. Treating patients with pre- or post-cerclage positive urogenital cultures did also not change GA at delivery. CONCLUSION: Positive urogenital cultures taken before clinically indicated cerclage intervention may be associated with lower GA at delivery. However, there seems to be no benefit of antibiotic treatment or routine urogenital cultures during follow-up of asymptomatic women after cerclage placement.

Subsequent fertility, pregnancy, and gynaecological and psychological outcomes after maternal-fetal surgery for open spina bifida: A prospective cohort study.

OBJECTIVE: To determine the medium-term maternal impact of open fetal spina bifida repair. DESIGN: Prospective cohort study. SETTING: University Hospitals Leuven, Belgium. POPULATION: Mothers who had open maternal-fetal spina bifida repair between March 2012 and December 2021. METHODS: A patient-reported survey on subsequent fertility, pregnancy, and gynaecological and psychological outcomes. MAIN OUTCOME MEASURES: Complications during subsequent pregnancies, and gynaecological and psychological problems. RESULTS: Seventy-two out of 100 invited women completed the questionnaire (72%). Despite being advised not to, seven of 13 women attempting to conceive became pregnant within 2 years after fetal surgery and one woman delivered vaginally. Two of the 16 subsequent pregnancies were complicated by an open neural tube defect. One pregnancy was complicated by a placenta accreta and one pregnancy was complicated by a uterine rupture, both with good neonatal outcomes. Nearly half of respondents who did not attempt to conceive reported that this was because of their experience of the index pregnancy and caring for the index child. Three out of four respondents reported medium-term psychological problems, mostly anxiety for the health of the index child, fear for recurrence in subsequent pregnancies and feelings of guilt. CONCLUSIONS: Open maternal-fetal surgery for spina bifida did not appear to affect fertility in our cohort. Half of the attempts to conceive took place within 2 years. One uterine rupture and one placenta accreta occurred in 16 subsequent pregnancies. Most respondents reported psychological problems linked to the index pregnancy, which reinforces the need for long-term psychological support.

Association between cervical length and gestational age at birth in singleton pregnancies: a multicentric prospective cohort study in the Brazilian population.

BACKGROUND: Short cervical length measured during the second trimester of pregnancy is an important risk factor for spontaneous preterm birth (sPTB). The aim of this study is to identify the association between mid-pregnancy cervical length (CL) and gestational age at birth in asymptomatic singleton pregnant women. METHODS: This is a prospective cohort study involving singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial) between July 2015 and March 2019. Transvaginal ultrasound to measure CL was performed from 18 to 22 + 6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks' gestation. For this analysis we considered all women with CL ≤ 30 mm receiving progesterone and a random selection of women with CL > 30 mm, keeping the populational distribution of CL. We obtained prognostic effectiveness data (area under receive operating characteristic curve (AUC), sensitivity and specificity and estimated Kaplan-Meier curves for preterm birth using different CL cutoff points. RESULTS: We report on 3139 women and identified a negative association between cervical length and sPTB. CL ≤ 25 mm was associated with sPTB < 28, sPTB < 34 and sPTB < 37 weeks, whereas a CL 25-30 mm was directly associated with late sPTB. CL by transvaginal ultrasound presented an AUC of 0.82 to predict sPTB < 28 weeks and 0.67 for sPTB < 34 weeks. Almost half of the sPTB occurred in nulliparous women and CL ≤ 30 mm was associated with sPTB at < 37 weeks (OR = 7.84; 95%CI = 5.5-11.1). The number needed to screen to detect one sPTB < 34 weeks in women with CL ≤ 25 mm is 121 and we estimated that 248 screening tests are necessary to prevent one sPTB < 34 weeks using progesterone prophylaxis. CONCLUSIONS: CL measured by transvaginal ultrasound should be used to predict sPTB < 34 weeks. Women with CL ≤ 30 mm are at increased risk for late sPTB.

[Diagnosis and management of a foetus with congenital high airway obstruction syndrome (CHAOS)]. / Cas clinique. Diagnostic et prise en charge d'un fœtus porteur d'un syndrome d'obstruction congénitale des voies respiratoires supérieures (CHAOS).

Congenital high airway obstruction syndrome is a rare malformation whose prognosis is very poor resulting in foetal or perinatal death if no perinatal intervention is performed. However, ultrasound and magnetic resonance enable an accurate prenatal diagnosis and optimal choice of interventional foetal medicine techniques (transtracheal puncture, fetoscopy). These approaches reduce foetal side effects related to the pathological process, and avoid the mother ex utero intrapartal treatment and its deleterious effects. If it becomes indispensable ex utero intrapartal treatment allows optimal management of the new born by securing the foetal airways while minimizing risk for hypoxic damage through the maintenance of maternal-foetal circulation. We present the story of a couple with a suspected case of CHAOS at 21 weeks of amenorrhea, the diagnostic and the management until the birth of the child.

Le syndrome d'obstruction congénitale des voies respiratoires supérieures est une malformation rare dont le pronostic est très péjoratif sans intervention périnatale, entraînant un décès in utero ou à la naissance. L'échographie et la résonance magnétique nucléaire permettent de poser un diagnostic prénatal précis et de choisir les techniques de médecine fœtale interventionnelle les mieux adaptées (ponction trachéale sous contrôle échographique, reperméabilisation sous fœtoscopie). Ces approches réduisent les effets secondaires fœtaux liés au processus pathologique, et évitent à la mère le traitement intrapartal ex utero et ses effets délétères. S'il devient indispensable, le traitement intrapartal ex utero permet une prise en charge optimale du nouveau-né en sécurisant ses voies respiratoires, tout en minimisant les dommages hypoxiques, grâce au maintien de la circulation materno-foetale. Nous présentons l'histoire d'un couple confronté à une suspicion de CHAOS à 21 semaines d'aménorrhée, le parcours diagnostique et la prise en charge jusqu'à la naissance de l'enfant.

Endothelial function and its determinants in children born after maternal bariatric surgery.

BACKGROUND: Children born from mothers who underwent bariatric surgery were found to have an improved lipid profile and lower CRP levels compared to siblings born before surgery. We hypothesized that surgery before pregnancy might also influence endothelial function in the offspring. METHODS: Blood sample analysis, blood pressure (BP) measurement, and peripheral arterial tonometry (PAT) were performed in 142 children (median age 10.5 years), either born from mothers who underwent bariatric surgery (BS) before pregnancy (n = 36) from mothers with overweight/obesity (OW/OB) (n = 71) or from normal weight (NW) mothers (n = 35), allowing the determination of the Reactive Hyperemia Index (RHI) in 111 children. RESULTS: Children of the BS group had a higher diastolic blood pressure SDS and a lower RHI compared to the children of the OW/OB and NW group (1.32 versus 1.37 in OW/OB and 1.70 in NW; p = 0.004). After log transformation and correction for age, weight SDS, BMI SDS, body fat percentage, and diastolic BP SDS, RHI was comparable between the groups. CONCLUSIONS: Children of mothers who underwent bariatric surgery before pregnancy do not have a disturbed endothelial function before puberty, when their increased diastolic BP and degree of adiposity is taken into account. IMPACT: Children born after maternal bariatric surgery have a higher diastolic blood pressure without impaired endothelial function. To our knowledge, this is the first study that investigates the vascular function of children based on maternal characteristics during pregnancy. Adult offspring of mothers with obesity during pregnancy have an increased cardiovascular mortality. Since we cannot demonstrate a childhood-onset primary vascular dysfunction, this cardiovascular vulnerability might be more related to the hypertension and body adiposity. Thus, more emphasis should be made on the prevention of obesity and hypertension in the offspring at risk for development of obesity.

Effect of the e-health supported INTER-ACT lifestyle intervention on postpartum weight retention and body composition, and associations with lifestyle behavior: A randomized controlled trial.

We investigated whether a postpartum lifestyle intervention reduced postpartum weight retention (PPWR) and improved body composition, and whether improved lifestyle was associated with less PPWR and improved body composition. A total of 1075 women with excessive gestational weight gain were randomized into the intervention (N = 551) or control (N = 524) group. A completion rate of 76% was reached. Anthropometrics and lifestyle data were collected at 6 weeks and 6 months postpartum. The e-health supported intervention consisted of 4 face-to-face coaching's, focusing on nutrition, exercise and mental wellbeing and using motivational interviewing and behavior change techniques. In the intervention group we observed; larger decrease in weight in women who reduced their energy intake (mean ± SD: 3.1 ± 4.2 kg vs. 2.2 ± 3.8 kg, P = 0.05) and decreased uncontrolled eating (3.5 ± 4.2 kg vs. 1.9 ± 3.7 kg, P ≤0.001) by the end of the intervention; larger decrease in fat percentage in women who reduced energy intake (2.3% ± 2.9 vs. 1.4% ± 2.7, P = 0.01), enhanced restrained eating (2.2% ± 3 vs. 1.4% ± 2.6, P = 0.02) and decreased uncontrolled eating (2.3% ± 2.9 vs. 1.5% ± 2.7, P = 0.01) and larger decrease in waist circumference in women who reduced energy intake (4.6 cm ± 4.8 vs. 3.3 cm ± 4.7, P = 0.01), enhanced restrained eating (4.5 cm ± 4.8 vs. 3.4 cm ± 4.8, P = 0.05) and decreased uncontrolled eating (4.7 cm ± 4.8 vs. 3.3 cm ± 4.8, P = 0.006), compared to those who did not. Improved energy intake, restrained eating and uncontrolled eating behavior were associated with more favorable outcomes in weight and body composition. ClinicalTrials.gov identifier:NCT02989142.

Validation of a food-frequency questionnaire to assess methyl-group donor intake in preschoolers.

A good assessment of dietary methyl-group donor intake (folate, choline, betaine, methionine) is needed to investigate the effect of methyl-group donor intake on children's health. The aim is to develop and validate a food-frequency questionnaire (FFQ) to estimate the daily intake of methyl-group donors in preschoolers. For the relative validity and reproducibility of the FFQ, a 7-day estimated dietary record (7d EDR) and repeated measurements 6 weeks apart (n = 77) were used respectively. For the validity (n = 75), a moderate ranking ability was obtained (de-attenuated Pearson correlation = 0.43-0.70; weighted ƙ 0.10-0.40), but the FFQ tends to overestimate the real intake. Cross-classification analysis showed that 38% (choline) and 28% (betaine) of the subjects were misclassified. The FFQ shows a moderate to good reproducibility, intra-class correlation coefficients range between 0.67 (betaine) and 0.76 (choline) with a maximal misclassification of 6.5% for betaine (weighted ƙ 0.37-0.69) (n = 77). CONCLUSION: The FFQ is a tool with a moderate validity and reproducibility to estimate the consumption of dietary methyl-group donors in preschoolers. This tool might be used in future research epidemiological studies including preschoolers. WHAT IS KNOWN: • Poor dietary habits during childhood have been associated with chronic disease in adulthood. • Methyl-group donors are important for DNA methylation, which is the underlying mechanism of disease development. WHAT IS NEW: • For the first time, a food-frequency questionnaire that can assess the intake of methione, folate, choline, and betaine has been developed and validated for the use in preschoolers.

Pulmonary hypertension in congenital diaphragmatic hernia: Antenatal prediction and impact on neonatal mortality.

OBJECTIVE: To determine the prevalence of pulmonary hypertension (PAH) in left-sided congenital diaphragmatic hernia (CDH); how we could predict it; and how PAH contributed to the model for mortality prediction. STUDY DESIGN: Retrospective analysis in three European centers. The primary outcome was the presence of PAH on postnatal day (d) 1, 7, and at discharge. Studied predictors of PAH were: observed/expected-lung/head-ratio (o/e LHR), liver-herniation, fetoscopic endoluminal tracheal occlusion (FETO), and gestational age (GA) at delivery. The combined effect of pre- and postnatal variables on mortality was modeled by Cox regression. RESULTS: Of the 197 neonates, 56 (28.4%) died. At d1, 67.5% (133/197) had PAH and 61.9% (101/163) by d7. Overall, 6.4% (9/141) had PAH at discharge. At d1, o/e LHR (odds ratio (OR) 0.96) and FETO (OR 2.99) independently correlated to PAH (areas under the curve [AUC]: 0.74). At d7, PAH significantly correlated only with the use of FETO (OR 3.9; AUC: 0.65). None were significant for PAH at discharge. Combining the occurrence of PAH with antenatal biomarkers improved mortality prediction (p = 0.02), in a model including o/e LHR (HR: 0.94), FETO (HR: 0.35), liver herniation (HR: 16.78), and PAH (HR: 15.95). CONCLUSIONS: Antenatal prediction of PAH was only moderate. The postnatal occurrence of PAH further increases the risk of death. Whereas this may be used to counsel parents in the postnatal period, our study demonstrates there is a need to find more accurate antenatal predictors for PAH.

The effects of dietary and lifestyle interventions among pregnant women with overweight or obesity on early childhood outcomes: an individual participant data meta-analysis from randomised trials.

BACKGROUND: The impact of maternal obesity extends beyond birth, being independently associated with an increased risk of child obesity. Current evidence demonstrates that women provided with a dietary intervention during pregnancy improve their dietary quality and have a modest reduction in gestational weight gain. However, the effect of this on longer-term childhood obesity-related outcomes is unknown. METHODS: We conducted an individual participant data meta-analysis from RCTs in which women with a singleton, live gestation between 10+0 and 20+0 weeks and body mass index (BMI) ≥ 25 kg/m2 in early pregnancy were randomised to a diet and/or lifestyle intervention or continued standard antenatal care and in which longer-term maternal and child follow-up at 3-5 years of age had been undertaken. The primary childhood outcome was BMI z-score above the 90th percentile. Secondary childhood outcomes included skinfold thickness measurements and body circumferences, fat-free mass, dietary and physical activity patterns, blood pressure, and neurodevelopment. RESULTS: Seven primary trials where follow-up of participants occurred were identified by a systematic literature search within the International Weight Management in Pregnancy (i-WIP) Collaborative Group collaboration, with six providing individual participant data. No additional studies were identified after a systematic literature search. A total of 2529 children and 2383 women contributed data. Approximately 30% of all child participants had a BMI z-score above the 90th percentile, with no significant difference between the intervention and control groups (aRR 0.97; 95% CI 0.87, 1.08; p=0.610). There were no statistically significant differences identified for any of the secondary outcome measures. CONCLUSIONS: In overweight and obese pregnant women, we found no evidence that maternal dietary and/or lifestyle intervention during pregnancy modifies the risk of early childhood obesity. Future research may need to target the pre-conception period in women and early childhood interventions. TRIAL REGISTRATION: PROSPERO, CRD42016047165.

Less sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women-a secondary analysis of the DALI study.

BACKGROUND/OBJECTIVES: Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women. SUBJECTS/METHODS: In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, <20 weeks gestation, with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m2, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24-28 weeks and 35-37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness. RESULTS: 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (-0.137; -0.210, -0.064 and -0.133; -0.202, -0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011). CONCLUSIONS: As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.

Determinants of changes in women's and men's eating behavior across the transition to parenthood: a focus group study.

BACKGROUND: During the pregnancy and postpartum period, both women and men experience physiological and psychological changes, which may negatively impact their eating behavior. A clear understanding of determinants of changes in eating behavior during this period is needed to facilitate the development of targeted family-based interventions countering unfavorable dietary changes during this critical life period. METHODS: Thirteen focus group discussions targeting determinants of changes in eating behavior during pregnancy and postpartum were conducted, involving a total of 74 expecting and first-time parents. A semi-structured question guide was used to facilitate the discussions. An inductive thematic approach was used to derive main and sub-categories of determinants from the data. The Determinants of Nutrition and Eating (DONE)-framework was employed to systematically organize and label the categories and determinants. RESULTS: Two frameworks were developed; one for the pregnancy and one for the postpartum period, comprising determinants of changes in eating behavior in both women and men. Three main levels of determinants were identified: (1) the individual level, including psychological (e.g., 'health consciousness'), situational (e.g., 'effort and convenience') and biological (e.g., 'discomfort'); (2) the interpersonal level (e.g., 'social influence') and (3) the environmental level, including micro- and meso/macro (e.g., 'home/environment food availability'). Determinants acting as barriers (e.g., 'time constraints') or facilitators (e.g., 'being a role model') were identified. Many determinants were mentioned during both (e.g., 'food knowledge') or just one investigated period (e.g., 'physiological changes' during pregnancy, 'influence of the baby' postpartum). Finally, some were described by both parents (e.g., 'self-regulation'), whereas others were mentioned by women (e.g., '(perceived) food safety') or men (e.g., 'other priorities') only. CONCLUSION: The developed frameworks set the foundation for the development of future family-based interventions and may be used already by healthcare providers to provide dietary guidance and support for women and men transitioning into parenthood. A focus on the interplay of individual factors at the biological and psychological level together with situational difficulties during pregnancy is recommended. Postpartum, focus should go to support first-time parents to obtain balance of both maintaining one's own health and taking care of the baby, on improving self-regulation skills, and on coping with related situational constraints.

The importance of maternal insulin resistance throughout pregnancy on neonatal adiposity.

BACKGROUND: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity. OBJECTIVES: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed. METHODS: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (<20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest. RESULTS: Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower mean sum of skinfolds compared to girls (20.3 mm, 95% CI 19.7, 21.0 vs 21.5 mm, 95% CI 20.8, 22.2). In boys, maternal HOMA-IR at <20 weeks was directly associated with neonatal adiposity (ß = 0.35 mm, 95% CI 0.01, 0.70). In girls, maternal HOMA-IR at 24-28 weeks was only indirectly associated with neonatal adiposity, which implies that this association was mediated via maternal HOMA-IR, glucose, triglycerides, and NEFA during pregnancy (ß = 0.26 mm, 95% CI 0.08, 0.44). CONCLUSIONS: The timing of the role of maternal insulin resistance on neonatal adiposity depends on fetal sex. Although the association was time-dependent, maternal insulin resistance was associated with neonatal adiposity in both sexes.

Ginger (Zingiber officinale) Root Extract During Pregnancy: A Clinical Feasibility Study.

There is almost no experience with concentrated ginger extracts during pregnancy. The purpose of this trial was to include 50 pregnant women in a clinical feasibility study with EXT.GR10, a 10 × concentrated ethanolic extract of ginger root. The primary objective was to detect complications in the mother during pregnancy and malformations or complications in the newborn at delivery. The secondary purpose was to evaluate the satisfaction of the patients. In total, 51 pregnant women were included in this observational study. They could freely use ginger tablets with a maximum of 2 tablets of 50 mg EXT.GR10 a day in case of gastrointestinal discomfort. Tablets were taken by 44 patients. Stillbirth, prematurity, hypertension, and gestational diabetes occurred. There were no serious complications at birth. In the newborn, 4 cases of dysplasia of the hip were seen and 2 minor malformations. There was no relation between events affecting mother and child and the number of EXT.GR10 tablets taken. About ⅔ of patients appreciated the effects of ginger. This is the first clinical study with the EXT.GR10 extract. Based on this feasibility study, a follow-up clinical trial is planned with a fixed minimum of exposure to EXT.GR10 during the first trimester of pregnancy.

The Detection, Outcome, and Presentation of Twin-Twin Transfusion Syndrome in Monochorionic Diamniotic Twin Pregnancies Followed with a Protocol of Fortnightly Ultrasound Examination.

BACKGROUND: Evidence to support a fortnightly scan protocol for monochorionic diamniotic (MCDA) pregnancies to detect twin-twin transfusion syndrome (TTTS) is scarce. Also, TTTS-related mortality in an unselected cohort is not well documented. Finally, common knowledge suggests that a more frequent follow-up may pick up the disease at a milder stage, but little is known on the ultrasound findings before the diagnosis. OBJECTIVES: We examine if a fortnightly ultrasound scan from 16 weeks onward detects TTTS in time. Also, we document the outcomes in a large unselected cohort of MCDA twins and examine the ultrasound findings within 14 days before diagnosis. METHODS: Retrospective cohort of 675 MCDA twin pregnancies followed with a fortnightly scan protocol from 16 weeks onward. Timely detection of TTTS was defined as before fetal demise (stage V), ruptured membranes, or a dilated cervix. We compared the ultrasound findings before the diagnosis between stage I-II and stage III-IV. RESULTS: A total of 82/675 (12%) pregnancies developed TTTS, of which 74/82 (90%) were detected in time. In 8/82 (10%), TTTS was diagnosed in stage V: 5 before 16 weeks and 2 after 26 weeks. Fetoscopic laser photocoagulation (FLP) of the placental anastomoses was performed in 48/82 (59%). The survival of TTTS in the entire cohort was 105/164 (64%). In contrast, survival after FLP was 77/96 (80%). In 16/19 (84%) of stage III-IV TTTS, abnormal Doppler findings preceded the diagnosis of TTTS. CONCLUSIONS: A scheme of fortnightly ultrasound scans from 16 weeks onward detects 9 out of ten TTTS pregnancies in time. Most stage V cases presented outside the typical time window of 16 and 26 weeks. Survival rates after FLP underestimate the mortality of TTTS. Most stage III-IV cases have abnormal Doppler findings before the diagnosis of TTTS.