BACKGROUND/OBJECTIVES:Umbilical cord leptin is increased in infants of women with obesity. We tested the hypothesis that a high cord leptin-to-fat mass ratio might be associated with adverse outcomes at birth and in early childhood. METHODS:A secondary analysis of vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention (DALI) trial was conducted. Cord leptin-to-fat mass ratios were classified into top (TT), middle, and low (LT) tertiles overall and within sexes. Relationship with neonatal outcomes and offspring BMI z-scores were compared between TT and LT groups. RESULTS:Among 323 infants (maternal pre-pregnancy BMI 33.7 ± 4.2 kg/m2, 52% male) female (vs. male) offspring had higher cord leptin, fat mass percentage, and leptin-to-fat mass ratio (median (IQR): 21.4 (13.4, 30.99) vs. 15.5 (8.3, 25.9), p < 0.001). Compared to the LT group, infants in the TT group (58% females) had higher cord leptin but similar fat mass percentage. Among males (but not in females), the C-peptide-to-glucose ratio was elevated in the TT group (vs. LT) (0.2 (0.1-0.2) vs. 0.1(0.02-0.2), p < 0.001), while birthweight (3.5 ± 0.5 vs. 3.7 ± 0.4 kg, p = 0.045), fat mass percentage (11.1 ± 3.9 vs. 13.0 ± 3.6, p = 0.008), and BMI z-scores (at age 1 only) were lower (median (IQR): -0.15 (-0.67, 0.98) vs. 1.35 (-0.06, 1.67), p = 0.03). CONCLUSIONS:Relative cord hyperleptinaemia was associated with reduced offspring BMI among males.

Pregnancy beyond the first trimester increases the risk of small bowel obstruction after Roux-en-Y gastric bypass, most often due to internal hernia. Surgical exploration can be challenging because of limited space and anatomical changes. Data on surgical and obstetrical outcomes are scarce. We identified 32 pregnant women who underwent surgery for small bowel obstruction following bariatric surgery at our institution between January 2014 and December 2024. Data were collected on bariatric surgery history, operative details, postoperative complications, and obstetric outcomes. All patients had a history of Roux-en-Y gastric bypass. Median gestational age at surgery was 23 weeks 0 days (IQR 17 + 3–29 + 6 weeks). The most common symptom was postprandial exacerbation of abdominal pain (74

INTRODUCTION:Hemoglobin Bart's hydrops fetalis syndrome (BHFS) is the most severe form of α-thalassemia, typically caused by homozygous deletion of α-globin genes. However, rare non-deletional variants, such as Hemoglobin (Hb) Agrinio, can also produce a lethal phenotype. CASE PRESENTATION:We report a case of homozygous Hb Agrinio (HBA2:c.89T>C, p.Leu30Pro) diagnosed prenatally in a fetus of Bulgarian origin presenting with hydrops and severe anemia at 23 weeks of gestation. Following diagnosis, the pregnancy was managed with five intrauterine transfusions, resulting in resolution of hydrops and prolongation of pregnancy to term. The neonate was delivered at 37+3 weeks, required transient respiratory and cardiovascular support, and remains clinically stable at 3 months of age under regular transfusion therapy. CONCLUSION:To our knowledge, this is only the second reported case of BHFS resulting from homozygous Hb Agrinio successfully managed with intrauterine transfusions, and uniquely, the first to achieve term delivery. This case highlights the importance of considering unstable α-globin variants in the differential diagnosis of unexplained fetal hydrops in an at-risk population. Early diagnosis and timely intrauterine transfusions can significantly improve the perinatal outcomes in these cases.

Objective: This study compared insertion difficulties, shunt failure, reintervention rates, maternal adverse events, and neonatal outcomes among different shunt types used in fetal hydrothorax. Method: A retrospective multicenter cohort study (2012-2022) was conducted across 12 international centers. The primary outcome was the occurrence of complications, classified as insertion difficulties and shunt failure (dislocation, occlusion, or unexplained shunt failure). Secondary outcomes included reintervention rates, maternal complications, and neonatal survival. Results: Among 349 cases, 345 were included in the analysis of the outcome measures. Rodeck shunts had significantly fewer complications (19.5%) compared to Somatex (38.3%, OR 2.53, p = 0.016) and Harrison shunts (50.0%, OR 3.82, p < 0.001). Somatex shunts had the highest rate of incorrect positioning (16%), while dislocation was most frequent with Harrison shunts (31.1%). Reintervention rates were lowest for Rodeck (12.1%) and highest for Harrison (32.2%). Maternal body mass index, fetal hydrops, laterality and year of shunt placement did not significantly influence complication rates. No significant differences in live birth rates or gestational age at delivery were observed. Conclusions: The Rodeck shunt was associated with fewer insertion difficulties, better shunt performance and lower reintervention rates. There was no difference in perinatal survival among the three shunt types.

BACKGROUND:Antenatal treatment with nipocalimab, a neonatal Fc receptor (FcRn) blocker, delayed or prevented fetal anemia, as compared with a historical benchmark, in a phase 2 study of early-onset severe hemolytic disease of the fetus and newborn (HDFN). We report on the fetal and neonatal pharmacokinetics of nipocalimab and infant immunity through 96 weeks after birth. METHODS:The UNITY study was a single-group, open-label study assessing pregnant individuals at high risk of early-onset severe HDFN treated with weekly intravenous nipocalimab (30 or 45 mg/kg) from 14 to 35 weeks' gestation, unless discontinued for safety-related stopping criteria or intrauterine transfusion initiation. Pharmacokinetics were assessed in maternal, fetal, and infant blood and colostrum or breast milk; FcRn receptor occupancy and immunoglobulin G (IgG) were measured in neonatal and maternal blood; and infant IgG and safety were monitored through 96 weeks after birth. RESULTS:Safety analysis included 12 live-born infants from 13 pregnancies (one fetal loss occurred following intrauterine transfusion complications). Nipocalimab concentrations were maintained in maternal participants at pharmacologically active concentrations (greater than 10 μg/ml) during the weekly dosing intervals, but were observed at low concentrations (10 μg/ml or less) in one of four fetal cordocenteses (0.04 μg/ml), one of 11 cord blood samples (0.7 μg/ml), three of seven colostrum samples (less than 4 μg/ml), and two of nine breast milk samples (less than 2 μg/ml). Low infant IgG at birth (cord blood median, 175 mg/dl; range, 92-941) reached levels consistent with a physiologic nadir by 24 weeks after birth (median, 273 mg/dl; range, 153-429) and recovered to normal range (with one exception) between 16 and 96 weeks (median, 762 mg/dl; range, 407-925). Infectious adverse events were primarily mild to moderate and typical for early childhood. Protective titers to age-appropriate vaccinations (diphtheria and tetanus) were observed in six of seven infants at or before 96 weeks. CONCLUSIONS:In this cohort of 12 live-born infants, antenatal treatment with nipocalimab resulted in low levels of detectable drug in fetal, neonatal, and infant samples. Treatment was associated with low IgG levels at birth; however, unusual or unexpected childhood illnesses or impaired vaccine responses were not observed. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT03842189.).

Excessive gestational weight gain (EGWG) poses significant health risks, including increased pregnancy complications, obesity, and metabolic disorders. Addressing EGWG is critical for women with a history of EGWG, as recurrence is common in consecutive pregnancies. This study presents findings from a subanalysis of the intervention arm of the INTER-ACT multi-center randomied controlled trial (RCT), which evaluated the impact of a combined mobile health (mHealth) and face-to-face lifestyle coaching intervention on EGWG recurrence during consecutive pregnancies. This subanalysis focuses on the intervention arm of the INTER-ACT RCT, conducted in six hospitals in Flanders, Belgium. The intervention consisted of two phases: the interpregnancy period (six weeks to six months postpartum) and the consecutive pregnancy (before 15 weeks post-conception to birth). Participants (n = 172) with a history of EGWG received health coaching and used an app to self-monitor weight, steps, and mental health. A multiple regression model assessed the effects of self-monitoring and coaching attendance on EGWG during the consecutive pregnancy in the intervention arm. App engagement decreased from 78

Endocrine-disrupting chemicals (EDCs) represent a threat for the ecosystem and human health. Exposure routes include modifiable exposures, such as choice of food or cosmetics but also daily habits such as airing the room. However, current attempts to reduce modifiable exposure often rely on knowledge provision and awareness-raising campaigns. This is the case even though human behaviour, decision making and habits change have been studied for a long time, and numerous psychological theories demonstrate that the transition from awareness of a health threat to actually change daily behaviour is not straightforward. This paper calls for interventions on EDCs exposure reduction to build on solid understanding of human behaviour and use of behaviour change techniques to achieve significant impact. We illustrate how this can be done by presenting the HYPIEND project, a multicomponent behavioural intervention designed to help pregnant women and prepubertal children (and their parents) to reduce their modifiable exposure to EDCs in these sensitive periods. HYPIEND relies on theoretical models such as the Health Action Process Approach (HAPA) model, motivational interviewing techniques, and broader support through partners (for pregnant women) and the school environment (for children) through a school-wide project built on the School Wide Positive Behavioural Interventions Supports.

OBJECTIVES:To describe haemolytic disease outcomes, growth, neurodevelopment and health-related quality of life (HRQoL) through 24 months of life in infants exposed to nipocalimab in pregnancies at high risk of early-onset severe haemolytic disease of the fetus and newborn (EOS-HDFN). DESIGN:A multicentre, open-label, single-arm trial. SETTING:Centres with expertise in HDFN management. PATIENTS:Pregnant individuals with previous EOS-HDFN and maternal anti-D titres ≥32 or anti-K titres ≥4. INTERVENTIONS:Weekly nipocalimab (30 and/or 45 mg/kg) from 14 to 35 gestational weeks. MAIN OUTCOME MEASURES:Infants' cord-blood alloantibody titres at birth, HDFN management, growth through 6 months, neurodevelopment (caregiver-reported Ages and Stages Questionnaire, third edition (ASQ-3)) and HRQoL assessments through 24 months of life. RESULTS:Of 13 pregnancies, 12 resulted in live births; one fetal loss occurred due to intrauterine transfusion (IUT) complications. A single simple transfusion was administered in one of seven infants delivered after a maternal nipocalimab course without IUTs, where cord blood alloantibody titres were <8. Multiple transfusions (one to seven simple transfusions/infant; one exchange transfusion) were administered to five infants delivered after early nipocalimab discontinuation and IUTs, with cord-blood alloantibody titres ranging from 512 to 32 768. No unusual growth patterns were observed through 6 months. No neurodevelopmental delays were identified through 24 months of life, with mean ASQ-3 domain scores within normal ranges. HRQoL outcomes were positive across physical, emotional, social and cognitive functioning. CONCLUSIONS:Maternal nipocalimab in pregnancies at high risk of EOS-HDFN may reduce adverse neonatal outcomes correlating with low cord-blood alloantibody titres, without affecting growth through 6 months, neurodevelopment or HRQoL through 24 months of life. TRIAL REGISTRATION NUMBER:NCT03842189.

Preterm birth (PTB) remains a significant public health concern despite advances in obstetric and neonatal care. Risk screening methods have modest predictive power, primarily because they rely on clinical risk factors that are not present in most women who experience a PTB. Unlike a single disease entity, PTB is a heterogeneous syndrome caused by various genetic, clinical, and environmental factors, and therefore, cannot be predicted by a single marker or risk indicator. For this reason, current risk assessment methods must be shifted from purely clinical indicators to ones that can also capture the underlying biology of the process. This expert opinion piece discusses the current state of risk screening in Europe and the importance of using a 'syndromic' rather than a 'single disease' view of PTB to guide future risk screening. A validated maternal serum biomarker test, marketed in the United States under the tradename PreTRM®, is also discussed as a tool that could potentially help address key shortcomings of risk screening methods, and thereby aid efforts to mitigate PTB, neonatal morbidity and mortality, and their associated costs.

BACKGROUND:One of the drawbacks of fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) is the need for a second intervention to establish airway patency. In this first-in-human study, we aimed to evaluate a novel tracheal occlusion device (Smart-TO) that spontaneously deflates when in close proximity to a strong magnetic field. METHODS:We conducted two parallel single-centre, single-arm, open-label trials in Paris, France, and Leuven, Belgium. Eligibility criteria included patient age 18 years or more, singleton pregnancy with CDH, and severe or moderate pulmonary hypoplasia in left-sided CDH; in Leuven, eligibility criteria also included severe hypoplasia in right-sided and bilateral CDH. Fetal lung size was assessed by measuring the observed-to-expected lung-to-head ratio by ultrasonography. Data for baseline demographics were self-reported and collected at the screening visit. Insertion of the Smart-TO balloon was scheduled between 27+0 weeks and 31+6 weeks of gestation. Balloon deflation was scheduled between 34+0 weeks and 34+6 weeks (or earlier, if clinically indicated) by exposure to the magnetic field of a MRI machine, and ultrasonography was then done to confirm balloon deflation. The primary endpoint was balloon deflation, with expulsion of the balloon from the fetal airways at birth as a coprimary outcome in the Paris arm of the study. The primary outcome was reported with its 95% CI using the continuity-corrected score method for all patients with the investigational medical device in place at the time of deflation. Safety analysis was conducted for all patients in whom FETO was attempted. These trials are registered with ClinicalTrials.gov (NCT04931212 [Paris]) and NCT05100693 [Leuven]) and have been completed. FINDINGS:Between Aug 4, 2021 and Jan 15, 2024, 48 patients were enrolled. Of these, 47 patients underwent FETO, and the Smart-TO was successfully placed in 46 fetuses. Median gestational age at FETO was 29+2 weeks (28+5-30+1 weeks). After placement, there was one spontaneous balloon deflation and one unexplained intrauterine fetal death. In all other patients, MRI machine-induced balloon deflation was attempted. The deflation rate was 100% (95% CI 92-100). At birth, the empty balloon was outside the airways in all infants. There were two cases of tracheomalacia in survivors, both with symptom resolution by the time of discharge from neonatal intensive care. There were 14 neonatal deaths, all attributed to pulmonary hypoplasia. Five adverse events were considered likely related to the device (of a total of 84), and no serious adverse events (of a total of 40) were related to the Smart-TO device. INTERPRETATION:This study shows effective magnetic resonance-induced deflation of the Smart-TO balloon and supports short-term safety. These findings constitute an important advance in fetal surgery for CDH, eliminating the need for a second intrauterine procedure. FUNDING:Clinical Council for Research and Education (Klinische Onderzoeks-en Opleidingsraad) of the University Hospitals of Leuven and Assistance Publique-Hôpitaux de Paris. Investigational devices (Smart-TO) were provided free of charge to patients and institutions by BS-MTI.

INTRODUCTION:Vitamin D (vitD) plays a role in metabolic regulation, including lipid metabolism and insulin sensitivity. During pregnancy, profound physiological changes in lipid handling and ketogenesis occur to support fetal development. However, the extent to which maternal vitamin D status influences these metabolic adaptations and fetal metabolic markers remains unclear. METHODS:In this secondary analysis, we examined lipid distribution throughout pregnancy-from before 20 weeks' gestation to delivery-in women with overweight or obesity, stratified by vitamin D status (deficiency, insufficiency, or sufficiency), assessing both maternal and cord blood. Main inclusion criteria were: age > =18 years, singleton pregnancy, < 20 weeks' gestation, BMI ≥ 29 kg/m2. Women with GDM < 20 weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (< 30 nmol/L, n = 102), insufficient (30-50 nmol/L, n = 222) and sufficient (> 50 nmol/L, n = 638) groups. VitD levels and lipid concentrations were assessed at < 20, 24-28 and 35-37 weeks' gestation and in cord blood. RESULTS:Compared with vitD sufficient women, women with vitD deficiency had significantly larger increases in LDL-C throughout pregnancy and ß-OH-butyrate at 24-28 weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher ß-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS:Early vitamin D deficiency before 20 weeks of gestation was associated with altered metabolic trajectories during pregnancy, including greater increases in LDL cholesterol and ketone body concentrations in women with overweight or obesity, as well as higher cord blood ketone levels in their offspring. These findings suggest that early maternal vitamin D status may influence maternal and fetal metabolic adaptations, although causal relationships and clinical implications require further investigation. TRIAL REGISTRATION:Trial registered at ISRCTN registry (https://doi.org/10.1186/ISRCTN70595832) trial number ISRCTN70595832. Registration date 02/12/2011.

BACKGROUND:Women of reproductive age represent a significant proportion of metabolic bariatric surgery (MBS) patients. However, research on their knowledge and perspectives regarding fertility and pregnancy post-MBS is scarce. METHODS:A questionnaire was developed to comprehensively capture women's perspectives on pregnancy after MBS. To ensure content validity, the survey was assessed by health care experts using content validity indices and through semi-structured patient interviews. The cross-sectional survey was then distributed via social media platforms. Responses from women aged 18-45, with a history of MBS were included for analysis. RESULTS:A 49-item questionnaire was developed and content validated. A total of 90 individuals completed the survey and met the inclusion criteria. The mean age was 30.8 ± 5.1 years. Seventy-five (83.3%) had undergone Roux-en-Y gastric bypass surgery. Regarding optimal timing and sequencing of MBS and conception, 24 respondents (26.7%) believed that women wishing to become pregnant should do so prior to undergoing MBS, while 40 (44.5%) did not share this view. In terms of risk-benefit perception, 40 respondents (44.4%) expressed concern about maternal health and 34 (37.8%) indicated concern about the potential impact on infant health following MBS. CONCLUSIONS:These findings highlight variability in perceptions regarding optimal timing of pregnancy relative to MBS, with a notable proportion of respondents expressing concerns about maternal and infant health. This underscores the need for evidence-based guidance for women of reproductive age considering MBS.

OBJECTIVES:To compare the 30-day outcomes of infants undergoing fetal versus postnatal repair of open spina bifida (OSB) who met the equivalent eligibility criteria. METHOD:A retrospective study of consecutive patients who underwent OSB repair (2018-2022) by a consistent pediatric neurosurgical team. All met the MOMS trial fetal surgery criteria. Primary outcomes included cerebrospinal fluid (CSF) complications, motor function, wound complications and non-neurosurgical neonatal complications within 30 days of birth. RESULTS:Among 109 myelomeningocele repairs (82 fetal and 27 postnatal), postnatal repairs had higher mean birthweight (3116.8 vs. 2477.8 g; p < 0.01) and gestational age at delivery (38 + 1 vs. 34 + 4 weeks + days; p < 0.01). Neonates with fetal repair were less likely to require hydrocephalus treatment (9% vs. 56%, p < 0.01) or have CSF leak (1% vs. 19%, p < 0.01). Wound infection (5.2% vs. 14.8%; p = 0.10) and dehiscence (2.6% vs. 14.8%; p = 0.09) rates were comparable. Respiratory distress syndrome was more frequent with fetal surgery (43% vs. 4%; p < 0.004), although neonatal intensive care (NICU) admission (34% vs. 26%) and neonatal hospital stay were comparable (fetal repair: 15.2 days ± 2.1 vs. postnatal repair: 14.8 days ± 3.1, p = 0.91). CONCLUSIONS:Open fetal repair was associated with earlier delivery but with comparable NICU and hospital stay and lower hydrocephalus treatment rate at 1 month of age.

Objective:To examine whether perceived usability of the INTER-ACT application influences postpartum weight loss and whether this effect is mediated by application use, motivational power, and implementation of lifestyle recommendations. Patients and Methods:Dutch-speaking women aged 18 years or older who had delivered a singleton infant and exceeded the recommended guidelines of the Institute of Medicine for gestational weight gain got recruited from May 2017 to April 2019, Across 6 Flemish hospitals. This secondary analysis included 138 participants of the INTER-ACT intervention arm. At 6 months postpartum participants completed a process evaluation survey, assessing application usability using the system usability scale, perceived motivational power, and perceived implementation of lifestyle recommendations. Weight loss was calculated between 6 weeks and 6 months postpartum. Pearson correlations and parallel mediation analyses were conducted, adjusting for maternal age, parity, and prepregnancy body mass index. Results:Application usability was moderate (mean system usability scale=60.6) and positively associated with perceived application use frequency (B=.05, P<.001), motivational power (B=.003, P<.001), and implementation of lifestyle recommendations (B=.01, P=.036), but not with weight loss. Usability showed no total, direct, or indirect effect on weight loss. Gestational weight gain (GWG) was the only significant predictor (B=0.24, P=.003). Higher usability was also associated with more positive and fewer negative emotional responses (P<.05). Conclusion:Application usability was associated with engagement and positive emotional experience, but not with reduced PPWR. The GWG remained the main determinant of postpartum weight outcomes. Preventing excessive GWG and complementing this with emotionally supportive postpartum mHealth tools may improve outcomes. Trial Registration:clinicaltrials.gov Identifier: NCT02989142.

OBJECTIVE:This study evaluates the procedural characteristics, complications, and outcomes of intrauterine transfusion (IUT) for fetal anemia caused by parvovirus B19 infection during the 2023-2024 epidemic in Northwestern Europe. METHOD:This multicenter observational study included all fetuses undergoing IUT for proven parvovirus B19-induced anemia at three tertiary fetal therapy centers in Northwestern Europe. Maternal, fetal, and procedural data were collected from electronic records. Technical challenges and complications were defined a priori. Primary outcomes were procedural characteristics and complications, prenatal neurological outcomes, and perinatal outcomes. RESULTS:A total of 93 IUTs were performed in 74 fetuses. Hydrops fetalis was present in 53%. Technical challenges occurred in 24% of procedures and complications in 18%. 59% of technical challenges and 65% of complications occurred in IUTs performed in hydropic fetuses. Intracranial hemorrhage (ICH) occurred in 10% of fetuses and was associated with lower preoperative hemoglobin (2.3 ± 0.6 g/dL vs. 4.4 ± 2.2 g/dL; p = 0.006). Perinatal survival was significantly lower following IUTs with complications (64%) compared with uncomplicated procedures (91%; p = 0.013). CONCLUSIONS:IUT for parvovirus B19-related fetal anemia is technically demanding, with complication rates exceeding prior reports. Complications and challenges significantly reduce perinatal survival. These findings underscore the importance of centralizing care in high-volume fetal medicine centers with experienced operators.

Objective To determine the incidence and clinical characteristics of surgical complications during pregnancy in women with a history of bariatric surgery.Design A nationwide, prospective, population-based cohort study.Setting High-risk obstetric care in Belgium: 67.6% of maternity units participated, covering 65% of all births in the study period.Participants Pregnant women with a history of bariatric surgery presenting with a surgical complication (internal hernia, intussusception, volvulus or adhesions; anastomotic ulcer or abscess; gastric band slippage or incisional hernia) between January 2021 and December 2022.Results 33 women experienced 35 surgical complications. Internal herniation was most common (n=25), predominantly following Roux-en-Y gastric bypass. Mean gestational age at diagnosis was 27+6 weeks. All women underwent surgical exploration within 24 hours; bowel resection was required in two cases. Caesarean section occurred in 48.5%, with 13 preterm births and one neonatal death. One woman required intensive care. No maternal death occurred.Conclusions Surgical complications following bariatric surgery in pregnancy are uncommon but carry significant obstetric risks. In this cohort, all reported complications occurred after procedures involving intestinal rerouting, predominantly Roux-en-Y gastric bypass. Prompt surgical management was associated with low maternal morbidity and no mortality, but frequently resulted in preterm birth and emergency caesarean section. These findings highlight the need for a low threshold for surgical evaluation of abdominal pain in pregnant women with previous bariatric surgery and support balanced counselling regarding the potential benefits and risks of different bariatric procedures in women of reproductive age.