# Why and How to Improve Nutritional Care for Pregnant Women after Bariatric Surgery: The NUMASURG Study Protocol.

Cécile Ciangura, Claire Rives-Lange, Bénédicte Lelièvre, Martine Laville, Marie-Aline Charles, Bérénice Ségrestin, Barbara Heude

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## To cite this version:

Cécile Ciangura, Claire Rives-Lange, Bénédicte Lelièvre, Martine Laville, Marie-Aline Charles, et al. Why and How to Improve Nutritional Care for Pregnant Women after Bariatric Surgery: The NUMASURG Study Protocol. Obesity Facts, 2025, pp.1-11. 10.1159/000545123. inserm-05302431

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# Why and How to Improve Nutritional Care for Pregnant Women after Bariatric Surgery: The NUMASURG Study Protocol

Cécile Cianguraª Claire Rives-Langeᵇ,ᶜ Bénédicte Lelièvreᵈ

Martine Lavilleᵉ Marie-Aline Charlesf, g Bérénice Ségrestinᵉ, h

Barbara Heudef on behalf of the NUMASURG Study Group

ªNutrition Department, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne Université, Paris, France; ᵇNutrition Department, Georges Pompidou European Hospital, AP-HP, Université Paris Cité, Paris, France; ᶜINSERM-INRIA-Université Paris Cité, UMR 1346, HeKA Team, Paris, France; ᵈPharmacology Toxicology Laboratory, Angers University Hospital, Angers, France; ᵉF-CRIN-FORCE (French Obesity Research Centre of Excellence), CARMEN Lab INSERM U1060/University of Lyon/INRA U1235, Lyon1 University, Lyon, France; ᵈParis Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS), Paris, France; ᵉINED, INSERM EFS, Joint Unit ELFE, Paris, France; ᵈEndocrinology-Diabetes-Nutrition Department, Hospices Civils de Lyon, Lyon, France

**Keywords**

Pregnancy · Child · Bariatric surgery · Micronutrients · Biomarkers

**Abstract**

**Introduction:** Pregnancies after bariatric surgery (BS) are considered at risk because of increased rate of maternal micronutrient deficiencies, small for gestational age, and prematurity. Longer-term data on child health are scarce and conflicting. The objective of the NUMASURG project is to understand the consequences of micronutrient deficiencies during pregnancy after BS for the mother and the offspring and to better document the child's health outcomes after maternal BS. **Methods:** NUMASURG is a collaborative project bringing together clinicians, biologists, epidemiologists, clinical researchers, and the French Obesity Research Center of Excellence network. The project is organized into four specific tasks: (1) establish a cohort of 1,000 pregnant women with a history of BS; (2) establish reference values for nutritional bio-

markers during pregnancy (vitamins A, B9, B12, 25[OH]-D, zinc, ferritin) from two birth cohorts of the French general population (EDEN and ELFE); (3) compare the nutritional status between pregnant women after BS and women from the general population and investigate the associations between nutritional biomarkers and small for gestational age and prematurity in both populations; and (4) describe the health of children born from mothers with a history of BS using the French national health data system. Started in September 2023, the project will run for 4 years. **Conclusion:** The NUMASURG project will allow for implementing updated recommendations concerning the monitoring and nutritional supplementation of pregnant women with a history of BS. Ultimate objective are to improve the nutritional status of these women and consequently limit the main risks currently observed during pregnancy after BS. Structuring a clinical database will help standardize practices and enable future research projects in this area and will be a key first step in creating a prospective cohort of children born from mothers with a history of BS.

© 2025 The Author(s).

Published by S. Karger AG, Basel
Introduction

Bariatric surgery (BS) is the most successful thera-
peutic option for patients with severe obesity and has
been increasingly performed worldwide [1–3]. This
treatment is associated with sustained weight loss,
amelioration and even remission of multiple comorbid-
ities, improved quality of life, and long-term reduction of
mortality [4, 5]. About 80% of people who undergo BS are
women, most of childbearing age [1]. Consequently, the
number of pregnancies after BS is increasing, especially
because weight loss improves spontaneous fertility [6]. BS
also reduces adverse outcomes of pregnancy such as
maternal hypertension, gestational diabetes, and mac-
rosomia [7, 8]. However, emerging evidence suggests that
BS is associated with an estimated doubling of the risk of
giving birth to a small-for-gestational-age (SGA) neonate
(weight ≤10th percentile for gestational age) and a
modest increase in premature births (birth term ≤37
gestational weeks [GWs]) [7, 8].

Micronutrient deficiencies are among the most com-
mon and compelling problems in people undergoing BS
[9]. However, micronutrients are essential for fetal de-
velopment, and deficiencies in some of them (mainly
iron, folates, vitamin B12, and zinc) have been associated
with SGA and/or prematurity [10–15]. BS-induced
changes in the digestive tract, such as intestinal shunt
and reduced gastric acidity and volume, may limit the
usual adaptive mechanisms developed during pregnancy
to increase micronutrient transfer to the fetoplacental
unit and meet the increased requirements during preg-
nancy [10, 16]. Therefore, surgery-induced maternal
nutritional deficiencies represent one of the main hy-
potheses for increased risk of SGA and prematurity after
BS but remains to be proven.

Specific guidelines emphasize the importance of monitoring maternal nutritional status and supplementation in this context [9,17–19]. However, disentangling whether a blood concentration of micronutrients corresponds to deficiencies requiring adjustment of supplementation or simply reflects the hemodilution physiologically induced by pregnancy may be difficult. Previous works have reported the absence of specific reference values during pregnancy for most of the micronutrients included in nutritional monitoring [17, 20]. Of note, this shortcoming also constitutes a major pitfall in terms of the risk of micronutrient overload when supplementing at high doses [11, 12, 21–23].

Although pregnancy after BS has become increasingly
common, little is known about whether and how ma-
ternal BS affects the development and health of the next

generation, in the mid and long term. Current literature
relying mainly on small sample size studies suggests that
maternal BS may modify offspring weight status and body
composition [24–26] as well as epigenetic, car-
diometabolic, immune, inflammatory, and appetite reg-
ulation markers [27–29]. Whether these modifications
translate to adverse clinical outcomes still needs to be
deciphered and more globally raises the question of the
benefit-risk balance of this treatment before pregnancy
with respect to the offspring’s health and development.

Therefore, there is a great need to better understand
the links between maternal nutritional status during
pregnancy, and fetal growth and offspring health and
development after BS. In this context, we have developed
the collaborative and multidisciplinary NUMASURG
(NUtritional MAternal biomarkers during pregnancy
and pregnancy and offspring outcomes: a study in the
general population and after bariatric SURGery) project,
with a main objective to better understand the conse-
quences of maternal nutritional deficiencies during
pregnancy and provide recommendations to improve
nutritional care in pregnant women with a history of BS.

Methods

The NUMASURG project is based on an original
collaboration between five academic and clinical teams
covering expertise in epidemiology, statistical analysis of
cohort and medical-administrative data, biology of mi-
cronutrients, clinical management of pregnant women
who had BS, and clinical research. It started in September
2023 and will be running for 4 years. This research was
funded by the MESSIDORE 2022 research project call,
the main objective of which was to financially support
multidisciplinary projects addressing clinical issues and
exploiting health data or existing biobanks.

NUMASURG is structured around the four following
specific objectives: (1) establish a cohort of 1,000 pregnant
women with a history of BS, gathering clinical and bi-
ological routine data (hereafter called the BS cohort); (2)
establish reference values of selected micronutrients
during pregnancy within the general population; (3)
investigate the associations between nutritional bio-
markers and birth outcomes in pregnant women from the
BS cohort and the general population; and (4) study the
postnatal consequences of BS for offspring in terms of
hospitalization and recourse to care. The project is or-
ganized into four corresponding complementary work
packages (WPs) as illustrated in Figure 1 and is described
in more detail below.
<figure><img src="image_3.png" /><figcaption>**Fig. 1.** Conceptual framework of the NUMASURG project on improving nutritional care for pregnant women after BS.</figcaption></figure>
<table><caption>**Table 1.** Data collected for the BS cohort, general population cohorts (EDEN and ELFE), and the French National Health Data System (SNDS) cohort</caption><thead><tr><th></th><th>BS cohort</th><th>EDEN</th><th>ELFE</th><th>SNDS</th></tr></thead><tbody><tr><td><strong>Bariatric surgery</strong><br>Type of surgery, date of surgery, time between surgery and pregnancy, complications</td><td>✓</td><td>Not considered</td><td>Not considered</td><td>✓</td></tr><tr><td><strong>Medical history</strong><br>Pregestational diabetes, pregestational hypertension, chronic illness, treatment</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td><strong>Sociodemographic factors</strong><br>Age, social insurance/social deprivation area, parity, height</td><td>✓<br>+ country of origin and profession</td><td>✓<br>+ country of origin, profession, and household income</td><td>✓<br>+ country of origin, profession, and household income</td><td>✓</td></tr><tr><td><strong>Lifestyle</strong><br>Smoking, alcohol or other toxic substance intake, dietary intake, micronutrient supplementation, medications</td><td>✓</td><td>✓<br>+ physical activity</td><td>✓<br>+ physical activity</td><td>Ø</td></tr><tr><td><strong>Maternal ponderal history</strong><br>Prepregnancy weight, gestational weight gain</td><td>✓<br>Weight before BS, before and during pregnancy, maximal in the life, and nadir after BS (medical record)</td><td>✓<br>Reported by the mothers</td><td>✓<br>Reported by the mothers</td><td>✓<br>Class of obesity during pregnancy only</td></tr><tr><td><strong>Father characteristics</strong><br>Smoking, weight, height, age</td><td>✓</td><td>✓</td><td>✓<br>+ dietary intake</td><td>Ø</td></tr><tr><td><strong>Nutritional status</strong></td><td>✓<br>Each trimester from first appointment: hemoglobin, ferritin, vitamin B12, folates, calcium, vitamin D and parathyroid hormone, albumin and prealbumin (transthyretin), retinol and retinol binding protein, prothrombin as proxy for vitamin K, ionography, zinc, selenium</td><td>✓<br>24-28 GWs Ferritin, vitamin B12, folates, vitamin D, retinol and retinol binding protein, zinc</td><td>✓<br>37-41 GWs Ferritin, vitamin B12, folates, vitamin D, retinol and retinol binding protein, zinc</td><td>Ø</td></tr><tr><td><strong>Biomarker analysis methods</strong></td><td>✓</td><td>✓</td><td>✓</td><td>Ø</td></tr><tr><td><strong>Ultrasound fetal growth parameters</strong></td><td>✓<br>22, 32, 37 GWs</td><td>✓<br>22, 32 GWs</td><td>✓<br>22, 32 GWs</td><td>Ø</td></tr><tr><td><strong>Pregnancy-related maternal outcomes</strong><br>Reproductive history, gravid hypertension, preeclampsia, gestational diabetes mellitus</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td><strong>Pregnancy-related obstetrical outcomes</strong><br>Miscarriage, stillbirth, termination of pregnancy, elective abortion, ectopic pregnancy, hydatidiform mole, delivery, cesarean, post-partum hemorrhage</td><td>✓</td><td>✓</td><td>✓<br>live births only</td><td>✓</td></tr></tbody></table>
<table><caption>**Table 1 (continued)**</caption><thead><tr><th></th><th>BS cohort</th><th>EDEN</th><th>ELFE</th><th>SNDS</th></tr></thead><tbody><tr><td><strong>Pregnancy-related neonatal outcomes</strong><br>Sex, birth weight, height, and head circumference, gestational age at birth, perinatal asphyxia, hypoglycemia, APGAR score, malformation, neonatal unit transfer, neonatal death</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td><strong>Maternal and neonatal post-partum outcomes</strong><br>At 2 months of life, weight and height of the neonate, breastfeeding, post-partum depressive symptoms, hospitalization</td><td>✓</td><td>✓</td><td>✓</td><td>Ø</td></tr><tr><td><strong>Child outcomes</strong><br>Hospital diagnoses, mortality, hospitalizations, number/type of medical and paramedical consultations</td><td>Ø</td><td>✓<br>Until 11 years</td><td>✓<br>Until 11 years</td><td>✓<br>Until 10 years + medication consumption</td></tr><tr><td colspan="5">GW, gestational week.</td></tr></tbody></table>

<table><caption>**Table 2. Summary of EDEN and ELFE birth cohorts**</caption><thead><tr><th></th><th>EDEN (Heude et al. [32], 2016)</th><th>ELFE (Charles et al. [31], 2020)</th></tr></thead><tbody><tr><td>Enrolled population</td><td>2,002 pregnant women from two regional university hospitals (Nancy, Poitiers) enrolled before 24 GWs</td><td>18,040 pregnant women from a representative sample of maternity units in mainland France enrolled at their child's birth after 33 GWs</td></tr><tr><td>Nutritional data</td><td>Prepregnancy weight reported by the mothers, measured height at clinical exam during pregnancy, food frequency questionnaire on usual diet before and in the last 3 months of pregnancy, gestational weight gain from obstetrical file</td><td>Prepregnancy weight and height reported by the mother, food frequency questionnaire on usual diet in the last 3 months of pregnancy, gestational weight gain reported by mother</td></tr><tr><td>Pregnancy outcomes</td><td>Recorded from obstetrical and infant medical files</td><td>Recorded from obstetrical and infant medical files</td></tr><tr><td>Socio-economic status and way of life</td><td>Maternal questionnaire during pregnancy and after delivery</td><td>Maternal questionnaire after delivery and at 2-month follow-up</td></tr><tr><td>Available biological samples for the project</td><td>1,700 plasma samples collected between 24 and 28 GWs and stored for 17-20 years at -80°C</td><td>2,100 plasma samples collected at delivery (33-41 GWs) and stored for 11 years at -196°C</td></tr><tr><td>More information</td><td>https://eden.vjf.inserm.fr</td><td>www.elfe-france.fr</td></tr><tr><td colspan="3">GW, gestational week.</td></tr></tbody></table>

## WP1: Establishing a Cohort of 1,000 Pregnant Women with a History of BS – The BS Cohort

In France, a large proportion of pregnant women with a history of BS are followed in Centers Specialized for Obesity (CSOs) [30]. We will extract relevant data

collected in clinical routine care from the medical files of these centers and set up a structured database. We previously conducted a survey of the 37 French CSOs to ensure data collection feasibility and discussed its results with our board consisting of scientists and healthcare
providers in order to consolidate the most relevant data to be collected. The data are listed in Table 1. We aim to prospectively include 1,000 singleton pregnant women over a 2-year period. If this number is not reached after 18 months, we will complete the cohort with retrospective data collection from women whose pregnancy occurred after 2019, the year that national guidelines for pregnancy management after BS were published in France [17]. We expect to enroll women who have had mainly sleeve or gastric bypass surgery, the two most common procedures in France, but all types of surgery could be included, including revisional surgeries (i.e., secondary bariatric interventions). Only data from routine care will be collected, and no specific intervention will be added. The detailed protocol and descriptive statistics of this BS cohort will be shared with the clinical and scientific community as a report or a scientific publication.

## WP2: Nutritional Biomarkers in Pregnant Women with and without a History of BS

This WP will rely on data and samples from two French birth cohorts, EDEN (Mother-child cohort on the prenatal and early postnatal determinants of child health and development) and ELFE (the French national cohort of children), that included women during pregnancy between 2003 and 2006 for EDEN or at delivery in 2011 for ELFE [31, 32]. Their study protocols have been described in detail elsewhere [31, 32] and are briefly presented in Table 2. These cohorts are important sources of biological collection and clinical data on mothers and offspring within the general population. Collected informations include lifestyle during pregnancy as well as pregnancy- and child-related outcomes and are listed in more detail in Table 1. Blood serum and plasma were collected between 24 and 28 GWs in EDEN and at delivery (between 33 and 41 GWs) in ELFE and frozen at -80°C. Constraints related to the quantity of available biological material from the above-mentioned cohorts and the cost of biological analyses necessitated the selection of limited number of nutritional markers for this specific objective: we will prioritize micronutrients for which maternal deficits have been consistently associated with severe neonatal or maternal consequences in the literature (within the general population), such as iron estimated by ferritin; folates; vitamins A, B12, and D; and zinc [11, 33].

As a preliminary step before conducting biological analyses, we will review the different analytic methods and select the most reliable and widely used techniques in routine care in laboratories. Reliability will be assessed by

inter- and intra-variability of the analytic methods, internal quality controls, and the external quality programs.

The samples from the EDEN and ELFE cohorts will be selected according to appropriate preanalytical criteria (e.g., time from collection to storage). About 1,500 serum and/or plasma samples in EDEN and about the same number in ELFE will be analyzed. Because of the large number of samples, they will be distributed among three hospital laboratories. To select the appropriate population of women from which reference values will be derived, we will exclude women with a history of BS, body mass index (BMI) <18 kg/m² or >25 kg/m², low diet quality (low adherence to the French nutritional recommendations from the Programme National Nutrition Santé [PNNS]), and pregnancy complications [34–36]. We will derive reference values, expressed as means, standard deviations, and percentiles using the Lambda-Mu-Sigma method at each available GW [37, 38]. This method is generally used to derive childhood growth references or standards [39, 40]. According to these references, we will derive thresholds permitting to define abnormal values and especially assess prevalences of deficiencies related to all micronutrients of interest in our BS cohort.

## WP3: Association between Nutritional Biomarkers and Birth Outcomes in Pregnant Women after BS and Women from the General Population

This WP will investigate the association between nutritional biomarker values during pregnancy and birth outcomes in both the BS and general population (all EDEN and ELFE women) cohorts. An essential primary step will be to better characterize the factors associated with variation in micronutrient concentrations in these two populations. Using multiple linear regression models, we will investigate potential determinants of variations among sociodemographic, lifestyle (including diet) or pregnancy-related factors, weight status, micronutrient supplementation, biological dosage methods used in routine care and factors specific to BS including type of surgery and time between surgery and pregnancy (Table 1). Correlations between concentrations of the different micronutrients will be described and the determinants of their covariation explored.

Second, outcomes of interest will be gestational age at birth and birth size for gestational age, considered both as continuous and binary variables (premature birth [before 37 GWs] and SGA [weight ≤10th percentile for gestational age]). The shape of the association between each micronutrient value and outcomes will be described by cubic splines to detect potential threshold or ceiling
effects in different groups depending on the dietary
supplementation history. Other potential determinants of
the outcomes will be identified in the literature and taken
into account by multivariable analyses after careful se-
lection by directed acyclic graphs [41]. Interactions be-
tween micronutrient values and prepregnancy BMI, type
of surgery, and other potentially relevant moderators will
be tested. The association between the combined status of
all micronutrients studied and outcomes will also be
explored using appropriate statistical techniques to take
into account their potential collinearity. Missing data will
be considered and imputation techniques applied when
appropriate. The number of participants in the general
and post-BS populations provides the necessary power
(80%) to identify a significant association (alpha risk of
5%), for example, between micronutrient deficiency and
risk of SGA, if this association exists and the odds ratio is
at least 1.7.

WP4: Consequences of a History of BS before
Pregnancy for Offspring

The objective of this WP is to compare pregnancy-
related complications and offspring outcomes for
mothers with or without a history of BS. We will use
comprehensive data from the French national health data
system (Système National des Données de Sante [SNDS]),
which covers 99% of people residing in France (>66
million inhabitants). This database provides a unique
anonymous identifier for each patient and since 2012
another identifier linking each newborn to their mother.
It contains administrative and demographic data, diag-
noses coded using the International Classification of
Diseases, 10th Revision [42], procedures performed in
private or public hospitals in France, and healthcare
consumption outside hospitals covered by the national
health insurance.

Outcomes for pregnancies with delivery beyond 22
GWs will include gestational diabetes, gestational hy-
pertension, preeclampsia or eclampsia, SGA, large for
gestational age (weight ≥90th percentile for gestational
age), termination of pregnancy, prematurity, stillbirth,
and perinatal mortality (<7 days of life). Outcomes for
pregnancies with delivery before 22 GWs will include
elective abortion, termination of pregnancy, ectopic
pregnancy, miscarriage, and hydatidiform mole. Out-
comes for long-term health of offspring (up to 10 years
of life) will include mortality, number and causes of
hospitalizations, number/type of medical and para-
medical consultations, and medication consumption.
Pregnancy- and birth-related outcomes of mothers with
or without a history of BS will be compared according to

two distinct and complementary study designs, as de-
scribed below.

For the first analysis, data for all women with post-BS
pregnancies occurring from January 2013 to December
2022, and their children, will be compared with data from
control pregnancies (and children) matched on end-of-
pregnancy date, age, BMI at pregnancy, pre-pregnancy
diabetes (type 1 and type 2), hypertension, socio-
economic status, and previous parity. The outcomes
listed above will be compared using generalized esti-
mating equations models.

For the second analysis, all women who had a preg-
nancy both before and after BS from January 2013 to
December 2022, and their children, will be included. Each
woman will then serve as her own control, and post-BS
pregnancies (and related children) will be compared to
pre-BS pregnancies (and related children) by using
conditional logistic regression models. A counterfactual
analysis using two consecutive pre-BS pregnancies will be
used to identify results that could be confounded by age
and parity changes from pre- to post-BS pregnancies.

Outcomes for children's long-term health will be
studied by comparing the frequencies of all child diag-
noses during hospitalizations, mortality, and healthcare
consumption by an outcome-wide association approach
in the two previous designs [43]. Multiple comparison
adjustments will involve using the false discovery rate
method. Mediation analysis will be used for child-related
outcomes to identify those potentially mediated by SGA
or prematurity. Subgroup analyses will involve the type of
BS, time from BS to pregnancy, and malnutrition from BS
to pregnancy.

Discussion

Expected Results

This ambitious collaborative project will provide im-
portant insights into the nutritional status of pregnant
women with a history of BS, the usual values of micro-
nutrients during pregnancy for comparison, and the
associations between BS, nutrition, and pregnancy and
child outcomes. It will allow for updating evidence-based
clinical practice recommendations for optimized nutri-
tional care of pregnant women after BS and hopefully
limit the risk of SGA, prematurity, and adverse long-term
outcomes. Finally, it will provide for the establishment of
a long-term routine clinical database that will serve as a
tool to optimize nutritional care for pregnant women
after BS. The multidisciplinary partners (epidemiology,
research, clinical, biology) have already worked and
collaborated in the field of BS and pregnancy or BS and micronutrient deficiencies [8, 17, 22, 44–46]. They are strongly involved in key research networks and scientific societies that will provide fertile ground for the wide dissemination and valorization of results at the national and international levels.

## Strengths and What This Project Will Add

Current evidence is scarce regarding the role of BS-induced malnutrition or micronutrient deficiencies in the increased risk of SGA and prematurity observed in women with a history of BS. Recent reviews on maternal nutrition during pregnancy after BS did not investigate or identify associations between micronutrient deficiencies and fetal growth [10, 16]. Some cohorts showed a negative association with risk of SGA when mothers received nutritional advice but only few associations with nutritional biomarkers, the main hypothesis being lack of power [22, 47, 48]. The organization of clinical care for patients with obesity around a CSO and the national coordination of the clinical research by the French Obesity Research Centre of Excellence (FORCE) are two strengths for the constitution of the BS cohort [30]. By combining the EDEN and ELFE general-population cohorts and the BS cohort, we expect data from approximately 4,000 women, including the dosages of at least ferritin; vitamins A, B9, B12, and D; and zinc, the value of which will cover two different periods of pregnancy, second and third trimesters. This unique worldwide dataset will provide substantial statistical power to thoroughly investigate the associations between micronutritional biomarkers and the risk of SGA or prematurity, within the specific context of BS.

Although physiological modifications mostly induced by hormonal variations in pregnancy are well established and associated with variations in biological values, most if not all laboratories provide no reference ranges specific to pregnancy. An exhaustive review of studies published between 1975 and 2008 provided reference values during pregnancy for a number of biomarkers [20]. The included studies were conducted in different geographical areas and ethnic groups, relied on discrepant pre-analytical conditions including various timing of blood samples and assay methods. Such heterogeneity may explain why the published usual values are too wide and not fully suitable to define micronutrient deficiency in clinical routine care. We believe that the large number of biological samples available from the EDEN and ELFE cohorts for two different periods of pregnancy, the screening of very healthy women, the attention to preanalytical conditions, and the restricted choice of reliable biological techniques

will allow for determining robust reference values during the second and third trimesters of pregnancy. These reference values are essential for the appropriate treatment of women exposed to deficiencies in the post-BS context while avoiding overdosing.

Previous studies of the health and development of children born to mothers with a history of BS mainly focused on weight and metabolic outcomes [24–26] and did not allow for demonstrating a protective effect of BS on childhood overweight and obesity risks. The recent Belgium EFFECTOR cohort of 36 children born after maternal BS enlarged the evaluated outcomes to eating habits [49], psychomotor and behavior outcomes [28], and endothelial function [50]. In NUMASURG, we will conduct analyses at a national scale, in real life, on a very large nonselected comprehensive population of more than 50,000 children born after BS, for the largest cohort from a medical-administrative database in this field to date. The absence of an a priori hypothesis will contribute to confirm associations already suggested in the literature and highlight new ones.

## Limitations

The first limitation is that selection biases may occur in both the EDEN and ELFE cohorts and the BS cohort. Indeed, participants from higher socio-economic levels are over-represented in population-based cohorts such as EDEN and ELFE [31, 32]. Regarding the BS cohort, exclusive recruitment from the CSOs may also select women particularly concerned by nutritional follow-up or conversely women who are referred because of a complex medical situation. Therefore, we will need to interpret our results with caution before the generalization of our recommendations. Finally, some limitations will be inherent to the nature of the SNDS database. We will not have exhaustive data on clinical aspects or the indication for reimbursed treatments, which will limit the search for certain diagnoses.

## Conclusion and Perspectives

The NUMASURG project will allow for determining the reference values and micronutrient targets during pregnancy and better understanding the consequences of maternal nutritional deficiency during pregnancy after BS. These new insights will allow for updating guidelines regarding the optimal set of maternal, obstetric, and pediatric clinical and biological factors to be monitored in routine care. These guidelines will detail how to assess the maternal nutritional status, the biological targets for micronutrients, and the supplementation protocols for preventing and correcting micronutrient deficiencies. We
hope that these recommendations will help limit the risks
of SGA and prematurity observed in pregnancy after BS
and improve long-term health outcomes. Structuring a
standardized clinical database within each CSO will
enable future research projects in this field and is a first
step in the constitution of a prospective cohort of children
born after BS.

Acknowledgments

The authors thank Mrs Nesrine Zaabar, Project Manager of FORCE Network, all clinicians in the CSOs, biological laboratories and obstetrics departments involved in the data collection of BS cohort. The authors thank the scientific coordinators (B. Geay, H. Léridon, C. Bois, J.L. Lanoé, X. Thierry, and C. Zaros), IT employees and data managers, statisticians (M. Cheminat, C. Ricourt, A. Candea, and S. de Visme), administrative and family communication staff, and study technicians (C. Guevel, M. Zoubiri, L.G.L. Gravier, I. Milan, and R. Popa) from the ELFE coordination team. The authors are also grateful to the families who gave their consent to participate in the EDEN and ELFE cohorts.

Statement of Ethics

The database of pregnancies after BS established in the CSOs will be hosted with all the security and accessibility requirements for personal data hosting in compliance with General Data Protection Regulation, after submission to the Scientific and Ethics Committee, along with a declaration of conformity to the required ethics regulation (MR004) to the French data protection authority (CNIL). Regarding the EDEN cohort study, written informed consent was obtained twice from parents: once at enrollment for their own participation and once after delivery for the participation of their child. The study received approval from the Ethics Committee (CCPPRB, No. 02-70) of Kremlin Bicêtre on 12 December 2002 and from CNIL (Commission Nationale Informatique et Liberté), the French data privacy institution. Implication of the EDEN cohort data and biological samples in the NUMASURG project has been approved by the EDEN steering committee on 12 October 2022.

Regarding the ELFE cohort study, written informed consent
was obtain from parents for their own and their child's partici-
pation after delivery. The ELFE study received approvals from the
Advisory Committee for the Processing of Information for Health
Research (Comité Consultatif sur le Traitement des Informations
pour la Recherche en Santé: CCTIRS; authorization 10.623), the
committee for protection of persons engaged in research (CPP:
Comité de Protection des Personnes; authorization CPP-IDF IX-
11-024), the National Data Protection Authority (Commission
National Informatique et Libertés: CNIL, authorization 910504),
and the National Council for Statistical Information (CNIS).
Implication of the ELFE cohort data and biological samples in the
NUMASURG project has been approved by the Elfe biological
subcommittee of the scientific council on 14 September 2023.

Regarding the SNDS, the project is registered with the SNDS
access rights authority and the Health Data Hub (No. 16515049).
The Health Data Hub and the National Health Insurance Fund
ensure subject information and rights compliance with the Public
Health Code (Article R1461-9). Ethical approval and consent were
not required as this study was based on publicly available data,
according to French regulation on research reusing the SNDS
database.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was supported by a grant from INSERM and the French Ministry of Health (Messidore 2022, No. 97 – innovative methodologies, devices, tools, and research in clinical trials using health data and biobanks). The EDEN study was supported by the Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A), and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l'Education Nationale – a complementary health insurance (MGEN), French national agency for food security, and French-speaking association for the study of diabetes and metabolism (ALFEDIAM). The ELFE survey is a joint project between the French Institute for Demographic Studies (INED) and the National Institute of Health and Medical Research (INSERM), in partnership with the French blood transfusion service (Etablissement français du sang, EFS), Santé publique France, National Institute for Statistics and Economic Studies (INSEE), Direction générale de la santé (DGS, part of the Ministry of Health and Social Affairs), Direction générale de la prévention des risques (DGPR, Ministry for the Environment), Direction de la recherche, des études, de l’évaluation et des statistiques (DREES, Ministry of Health and Social Affairs), Département des études, de la prospective et des statistiques (DEPS, Ministry of Culture), and Caisse nationale des allocations familiales (CNAF), with the support of the Ministry of Higher Education and Research and the Institut national de la jeunesse et de l’éducation populaire (INJEP). Via the RECONAI platform, it receives a government grant managed by the National Research Agency under the “Investissements d’avenir” program (ANR-11-EQPX-0038). The funders had no role in the design, data collection, data analysis, and reporting of this study.
## Author Contributions

C.C., C.R.-L., B.L., M.L., M.-A.C., B.S., and B.H. designed the research and contributed to fundraising. Members of the NUMASURG study group participated in the conception of the project. C.C. and B.H. wrote the first draft of manuscript. All authors reviewed the draft, provided critical feedback, and approved the final version of the manuscript. The NUMASURG study group members are cited in the online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545123).

## Data Availability Statement

The data used in this project will not be made publicly available as they are personal data containing sensitive information. However, data access may be granted upon reasonable request by contacting the corresponding author. Each request will be reviewed by a cohort-specific steering committee, and data-sharing agreements ensuring compliance with GDPR regulations will be signed between the parties.

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