M Linard

Béatrice Blondel

C Estellat

C Deneux-Tharaux

D Luton

J F Oury

T Schmitz

L Mandelbrot

Elie Azria
email: eazria@hpsj.fr

Pierre François Ceccaldi

Catherine Crenn-Hebert

Philippe Ravaud

Association between inadequate antenatal care utilisation and severe perinatal and maternal morbidity: an analysis in the PreCARE cohort

Keywords: prenatal care, pregnancy complications, severe maternal morbidity, severe perinatal morbidity, ultrasounds, APNCU index Inadequate antenatal care utilisation is associated with severe maternal and perinatal morbidity

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Routine antenatal care is one of the most widely recommended measures to prevent pregnancy complications. It has progressively been recognised by health-care providers as effective since its development in the 1900s, despite the absence of adequate scientific evaluation.(1,2) Its evaluation today is not easy. In developed countries, which have already adopted antenatal care, both medical staff and women are reluctant to participate in randomised trials. [START_REF] Dowswell | Alternative versus standard packages of antenatal care for low-risk pregnancy[END_REF] Observational studies report inconsistent results about its effectiveness in reducing perinatal morbidity [START_REF] Barros | Role of prenatal care in preterm birth and low birthweight in Portugal[END_REF][START_REF] Partridge | Inadequate Prenatal Care Utilization and Risks of Infant Mortality and Poor Birth Outcome: A Retrospective Analysis of[END_REF][START_REF] Heaman | Inadequate prenatal care and its association with adverse pregnancy outcomes: A comparison of indices[END_REF][START_REF] Vanderweele | A comparison of four prenatal care indices in birth outcome models: comparable results for predicting small-for-gestational-age outcome but different results for preterm birth or infant mortality[END_REF][START_REF] Petrou | Antenatal visits and adverse perinatal outcomes: results from a British population-based study[END_REF][START_REF] Beeckman | The relationship between antenatal care and preterm birth: the importance of content of care[END_REF][START_REF] Fiscella | Does prenatal care improve birth outcomes? A critical review[END_REF], while the association between antenatal care utilisation (ACU) and maternal morbidity has been examined less extensively. [START_REF] Nair | Risk factors and newborn outcomes associated with maternal deaths in the UK from 2009 to 2013: a national case-control study[END_REF][START_REF] Maupin | Characteristics of women who deliver with no prenatal care[END_REF] These discrepancies might reflect various methodological difficulties, including the need for a large sample size with accurate data about numerous components of antenatal care, and the large number of confounding factors that must be taken into account.

This absence of evidence has led to wide variations in national recommendations and policies throughout the world. The recommended number of antenatal visits ranges from a minimum of four for the World Health Organisation [START_REF]Standards for Maternal and Neonatal Care -Provision of effective antenatal care[END_REF] to 15 for the American Congress of Obstetrics and Gynecology. [START_REF]Guidelines for Perinatal Care, Seventh Edition[END_REF] France, like several other European countries [START_REF]Antenatal care for uncomplicated pregnancies -26[END_REF], recommends an intermediate number, eight. [START_REF]Antenatal care for uncomplicated pregnancies -26[END_REF][START_REF] Has | Suivi et orientation des femmes enceintes en fonction des situations à risque identifiées[END_REF][START_REF] Schott | Four countries, four ways of discussing low-risk pregnancy and normal delivery: In France, Germany, the Netherlands, and the United Kingdom[END_REF] Moreover, although consensus exists on the performance of some testssuch as blood pressure measurement or rhesus factor determination, recommendations differ not only about the numbers and timing of antenatal visits but also their content. [START_REF] Bernloehr | Antenatal care in the European Union: A survey on guidelines in all 25 member states of the Community[END_REF] Several countries advise only one ultrasound, while France counsels three for routine antenatal surveillance. These differences highlight the need to evaluate different models of antenatal care, especially as most of the assessments in developed countries have taken place in North America. [START_REF] Buekens | A comparison of prenatal care use in the United States and Europe[END_REF] Conducting a secondary analysis of the French multicentre PreCARE cohort study, we aimed to assess the association between the adequacy of antenatal care utilisation and both severe maternal and perinatal morbidity in France. Initially designed to study the impact of maternal social deprivation on maternal and perinatal outcomes, this cohort makes it possible to control for many social and medical characteristics that are potential confounders in the analysis of the independent impact of antenatal care on health.

Methods

Study design, setting and participants

The PreCARE prospective multicentre cohort study [START_REF] Gonthier | Impact of maternal social deprivation on prenatal care utilization: the PreCARE cohort study[END_REF] took place in four maternity units in university hospitals located in a geographical area characterised by a high prevalence of social deprivation in the area of northern Paris and its adjoining suburbs (France). Participants were all adult women registered to deliver or who delivered between 2010 and 2012 in these units (n=10 419).

Inclusion occurred from the first point during the pregnancy that the woman entered in contact with the hospital. Women and newborns were followed from inclusion through hospital discharge after delivery.

For this secondary analysis, we restricted the study population to women with singleton pregnancies who gave birth after 21 completed weeks of gestation. We also excluded in utero transfers from nonparticipating maternity units. Women who gave birth in a non-participating hospital, were lost to follow-up, or had completely empty questionnaires were excluded (Flow chart in Figure S1).

The regional review board (CPP-Ile-de-France III, N° 09.341bis, date of approval: November 19,

2009

) approved the study. Each woman provided oral informed consent, in compliance with French law.

Data collection

Participants were asked to complete two self-administered questionnaires, one at inclusion and one during the postpartum period before discharge. These questionnaires were available in four languages.

A research assistant or interpreter provided assistance when needed. Some data on ACU came from the postpartum questionnaire; research assistants collected the rest from the women's medical files.

Women's medical history and details of their pregnancies were collected both by research assistants and the practitioners who performed the delivery or midwives caring for them during the postpartum hospitalisation. Data about socioeconomic factors came from the self-administered questionnaires.

Antenatal care characteristics

Several components were measured: 1) late initiation of antenatal care (after 14 weeks), 2) rate of completed visits on recommended visits according to gestational age at delivery, considering both scheduled outpatient and inpatient visits. Visits for control of maternal blood pressure or fetal heart monitoring were not taken into account in the numbers of visits.

3) The absence of the ultrasounds recommended in the first (at 11-14 weeks), second (21-24 weeks) and third trimesters (31-34 weeks).

We also adapted the most common index of ACU reported in the literature: the Adequacy of Prenatal Care Utilization index (APNCU) [START_REF] Kotelchuck | An evaluation of the Kessner Adequacy of Prenatal Care Index and a proposed Adequacy of Prenatal Care Utilization Index[END_REF][START_REF] Alexander | Quantifying the adequacy of prenatal care: a comparison of indices[END_REF] to create two modified indexes: mAPNCU-1 and mAPNCU- The mAPNCU-2 further incorporated the recommended ultrasounds: some women with missing ultrasounds were reclassified to the inadequate category (if the first trimester ultrasound or both of the latter ultrasounds were missing) or the intermediate category (if only the second or the third ultrasound was missing) (Figure S2).

Outcome measures: Severe maternal and perinatal morbidity

Severe maternal morbidity (SMM) was defined by at least one of the following complications: haemorrhagic shock, severe postpartum haemorrhage (second-line uterotonic treatment associated with transfusion of at least two units of packed red blood cells, and/or uterine artery ligation, and/or uterine compressive sutures, and/or embolization, and/or hysterectomy), eclampsia, abruptio placenta, severe pre-eclampsia (SBP>160 mm Hg, DBP>110 mm Hg, or hypertension with general signs, and one or more of the following: proteinuria >3.5 g/24 h, serum creatinine >100 µmol/l, diuresis <20 ml/h, haemolysis, ASAT >3N, thrombocytopoenia <100 000/mm3, or before 32 weeks), severe sepsis (sepsis with organ failure), convulsions, diabetic ketoacidosis, deep venous thrombosis or pulmonary embolism, grade 3 or 4 perineal trauma, uterine rupture, intensive care unit (ICU) admission, surgical re-intervention, or maternal death.

Severe perinatal morbidity (SPM) included at least one of the following complications: very preterm birth (before 32 weeks), birth weight below the third percentile, fetal death (including medical termination of pregnancy), neonatal death (< 28 days and before discharge), neonatal trauma (except collarbone fracture), brachial plexus strain, meconium aspiration syndrome, neonatal convulsions, 5minute Apgar score < 3 or umbilical cord pH< 7.

Covariates

Data were collected about socio-demographic characteristics (age, education, mother's country of birth and social deprivation), health status (number of previous pregnancies, body mass index and medical history), behaviour (tobacco consumption) and maternity unit of delivery.

A binary variable assessing the medical risk level at the beginning of pregnancy was created based on the presence or absence of a high risk, in accordance with French guidelines [START_REF] Has | Suivi et orientation des femmes enceintes en fonction des situations à risque identifiées[END_REF]. It took into account history of cardiac disease, hypertension, diabetes, venous thrombosis, pulmonary embolism, Graves' disease, asthma, homozygous sickle cell anaemia, thrombocytopoenia, coagulation disorder, a rare or systemic disease, nephropathy, HIV infection, late miscarriage, pre-eclampsia, growth restriction, preterm delivery, fetal death or neonatal death. We did not, however, adjust for medical risk during pregnancy or gestational age because we considered them to be intermediate factors in the association between ACU and severe morbidity.

As Opatowski et al. [START_REF] Opatowski | New index of social deprivation during pregnancy: results from a national study in France[END_REF] suggested, maternal social deprivation at the beginning of pregnancy was characterised by a quantitative index including four dimensions: 1) social isolation; 2) unstable or insecure housing conditions; 3) main household income not due to paid work (that is, income from public assistance, relatives, friends, or charitable organisations); 4) lack of standard health insurance (no health care insurance, health care insurance provided to women with an unauthorised immigration status or provided to those ineligible for standard public health insurance because unemployed or not in the labour force or assignee status). For women with missing data on these four dimensions at the beginning of pregnancy, data were imputed with data collected in post-partum when available (n=81).

Statistical analysis

First we compared the characteristics of the women included in the analysis to those of the women excluded for insufficient data. Then we compiled descriptive statistics about the study population's characteristics, their ACU and the prevalence of severe morbidity. Logistic regression models were then used to assess the associations between each component of ACU taken separately and SMM or SPM in the study population. The variables introduced into the models were those clinically relevant or commonly found in the literature. The linearity of the association of the quantitative variables (age, body mass index and number of previous pregnancies) with ACU was tested; when the association was not linear, the variables were categorised. Maternity unit effects were handled as fixed effects.

Goodness-of-fit was assessed by the Hosmer-Lemeshow test.

The missing data rates for the variables included in the multivariate model ranged from 0 to 4.8%

(Table S1). To impute these data, we performed multiple imputations by chained equations (Details in Table S2).

We presented the results of the imputed models as adjusted odds ratios (aOR) with their 95% confidence intervals (95% CI). The results of the complete cases analyses are available in Table S2.

All statistical tests were two-tailed and the threshold for statistical significance was set at a probability value of <.05.

Analyses were performed with Stata® software, version 12.1 (Stata Corporation, College Station, TX, US).

Results

Among the 10 576 women asked to participate in the PreCARE study, 10 419 agreed (98.5%).

Because 613 women met at least one exclusion criterion for this analysis, 559 gave birth in a nonparticipating maternity unit or were lost to follow-up and 64 had completely empty questionnaires, our final study sample comprised 9117 women (Flow chart in FigureS1). Compared to women included in the analysis, those who delivered in other units, were lost to follow-up or had completely empty questionnaires (N= 623) were more often underprivileged, born in sub-Saharan Africa, and primiparous; they also had more often a body mass index <18.5 kg/m² and a low risk at the beginning of pregnancy (Table S3). Table 1 presents the main characteristics of the study sample.

The median number of scheduled antenatal visits was 9 (interquartile range: 8-11) and nearly half the women had more than 110% of the recommended number of visits (for their duration of pregnancy).

Nevertheless, 12.2% of participants had fewer than 80% of the recommended number of visits, and 17.0% began antenatal care at 14 weeks' gestation or later. Moreover, 21.6% of the women did not have a first trimester ultrasound and about 16% missed either the second or third trimester ultrasound.

Thus, 18.5% had inadequate antenatal care according to the mAPNCU-1 index, and 34.6% according to the mAPNCU-2 index, which also considered ultrasound examinations (Table 2).

SMM occurred in 259 women (2.91%). The main maternal complications were severe pre-eclampsia (0.80%), grade 3 or 4 perineal trauma (0.64%), and severe postpartum haemorrhage (0.52%) (Table 3).

SPM affected 494 newborns or fetuses (5.47%). The principal were birth weight below the third percentile (2.96%), very preterm birth (1.11%) and fetal death (0.68%) (Table 3).

The bivariate analyses presenting the factors associated with SMM or SPM are available in Tables S4 andS5. Medical risk level at the beginning of pregnancy, social deprivation, maternal country of birth, body mass index and number of previous pregnancies were associated with SMM. SPM was associated with each of those factors except social deprivation, as well as with maternal age, education level, and tobacco consumption.

Table 4 shows the results of the bivariate and multivariate analyses of the associations between various measures of ACU and both SMM and SPM. SMM was associated with a consultation rate of less than half the recommended visits, but not with late initiation of care, absence of ultrasounds, or inadequate ACU according to either mAPNCU index. Conversely, SPM was associated with all components of ACU (except late initiation of antenatal care). Women with fewer than either 50% or 50-79% of the recommended visits were at higher risk of SPM than women with 80-109% of them.

Missing any ultrasound examination was associated with an increased risk of SPM, while late initiation of antenatal care was not. When we considered the mAPNCU indexes, intermediate ACU according to mAPNCU-1 and inadequate ACU according to mAPNCU-2 were associated to SPM.

We found no interaction between antenatal care and social deprivation, pre-existing medical risk level, number of previous pregnancies or mother's country of birth. There was no major difference between analyses with imputed and non-imputed data (see Table S2 ).

Discussion

Main findings

Our results show inadequate ACU, defined by an index including late initiation of care, low consultation rate, and absence of some recommended ultrasounds, among 34.6% of the study population. After controlling for other maternal characteristics, inadequate ACU was associated with SMM and SPM, to degrees that vary with the component of care and the outcome considered. Late initiation of care was not associated with severe morbidity. A rate below 50% of the recommended number of visits was associated with an increased risk of both SMM and SPM. Missing an ultrasound scan was associated only with SPM.

Strengths and limitations

The main strengths of our study are its large sample size, multicentre nature and prospective design.

We assessed several components of ACU and highlighted their individual associations with SMM and SPM. In addition, the use of a modified APNCU index allowed us to assess the adequacy of ACU according to French policies.

As the number of recommended antenatal visits was defined based on guidelines for low risk pregnancies, the prevalence of ACU may be biased for women with a high risk pregnancy, underestimating inadequate ACU and overestimating adequate + ACU. Yet, the differential between the number of recommended visits for low and high risk women was probably reduced by the fact that most of prenatal visits added in case of high risk pregnancy are visits for control of maternal blood pressure or fetal heart monitoring and these visits were not taken into account in the numbers of visits.

Furthermore, in the multivariate analysis, OR were adjusted for the medical risk level at the beginning of pregnancy. However, this phenomenon, if it exists, would lead to classifying women "exposed" to the inadequate ACU as "unexposed", and underestimating the association studied; it would not call into question the observed result, ie the significant association between inadequate ACU and morbidity.

To estimate the association between ACU and severe morbidity, we used a composite variable of severe morbidity. This method enabled us to assess the impact of ACU on SMM and SPM more globally and to take into account outcomes with a prevalence too low to allow them to be studied individually. This approach seems appropriate as we hypothesise that ACU might have an impact on each of these morbidities by providing prevention advice, explaining warning signs, screening for complications and providing care. We chose to focus on severe morbidity so that we could examine the potential impact of ACU on both the onset and the worsening of maternal and perinatal morbidity, given that most complications can only be screened for or treated but not prevented.

Despite an adjustment for major confounding factors [START_REF] Nair | Risk factors and newborn outcomes associated with maternal deaths in the UK from 2009 to 2013: a national case-control study[END_REF][START_REF] Gonthier | Impact of maternal social deprivation on prenatal care utilization: the PreCARE cohort study[END_REF][START_REF] Beeckman | Determinants of the number of antenatal visits in a metropolitan region[END_REF][START_REF] Delvaux | Barriers to prenatal care in Europe[END_REF][START_REF] Jong | Determinants of late and/or inadequate use of prenatal healthcare in high-income countries: a systematic review[END_REF][START_REF] Fobelets | Predictors of late initiation for prenatal care in a metropolitan region in Belgium. A cohort study[END_REF] , the risk of residual confounding related to our observational design is the main limit of our study; some confounding factors related to psychological profile or health behaviour may remain.

The availability of the questionnaires in four different languages, and help for completing it reduced the risks of bias and the rate of missing data. Nevertheless, the substantial number of women excluded for missing data remains a limitation of the study. Because these women were more often underprivileged and born abroad than the final sample, we hypothesise that it might have underestimated the strength of the association as they are more likely to have inadequate antenatal care [START_REF] Gonthier | Impact of maternal social deprivation on prenatal care utilization: the PreCARE cohort study[END_REF] and pregnancy complications. [START_REF] Azria | Social inequalities in maternal health[END_REF] Another limitation of this study is related to the high prevalence of underprivileged women and women born abroad compared to the national profile [START_REF] Blondel | La santé périnatale en France métropolitaine de 1995 à 2010. Résultats des enquêtes nationales périnatales[END_REF], which limits the generalisability of our results.

Interpretation

The assessment of ACU revealed two different trends: first, as previously reported in other developed countries [START_REF] Partridge | Inadequate Prenatal Care Utilization and Risks of Infant Mortality and Poor Birth Outcome: A Retrospective Analysis of[END_REF][START_REF] Heaman | Inadequate prenatal care and its association with adverse pregnancy outcomes: A comparison of indices[END_REF][START_REF] Beeckman | Determinants of the number of antenatal visits in a metropolitan region[END_REF][START_REF] Blondel | La santé périnatale en France métropolitaine de 1995 à 2010. Résultats des enquêtes nationales périnatales[END_REF][START_REF] Backe | Overutilization of antenatal care in Norway[END_REF], high percentage of women appear to be having more than the recommended number of visits; second, the percentage of inadequate antenatal care is higher than in similar studies.

The prevalence of late initiation of care was 17.0%, versus 6.1% in Belgium.( 27) Compared with the 2010 National Perinatal Survey (29), our number of antenatal visit and our rate of first trimester ultrasounds seem to be both lower; they were, however, concordant with the results of a study conducted in the area of northern Paris. [START_REF] Azria | Improvement of firsttrimester ultrasound screening in socially deprived settings through a community-based perinatal network[END_REF] This might be explained by the high prevalence of underprivileged and migrant women in our study sample.(

The prevalence of severe morbidity was consistent with previous studies in France, [START_REF] Blondel | La santé périnatale en France métropolitaine de 1995 à 2010. Résultats des enquêtes nationales périnatales[END_REF][START_REF] Bouvier-Colle | Severe maternal morbidity : differences between women's intensive care admissions and maternal deaths in the Ile-de-France health areas[END_REF][START_REF] Pommereau-Lathelize | Severe neonatal acidosis: comparison and analysis of obstetrical practices in two French perinatal centers[END_REF][START_REF]European Perinatal health report. The health of pregnant women and babies in Europe in 2010: Euro-Peristat project with SCPE and Eurocat[END_REF](35)[START_REF] Chantry | Pregnancy-related ICU admissions in France: trends in rate and severity, 2006-2009[END_REF] which estimated rates of severe preeclampsia, severe perineal trauma, birth weight below the third percentile and very preterm birth at respectively 0.8%, 0.8%, 3.1% and 1.5%.

Two studies have previously reported an association between a small number of visits and perinatal morbidity: Petrou(8) described it for low birth weight, admission to neonatal ICU, and perinatal mortality, and Raatikainen [START_REF] Raatikainen | Under-attending free antenatal care is associated with adverse pregnancy outcomes[END_REF] for low birth weight, fetal and neonatal deaths. Bouvier-Colle [START_REF] Bouvier-Colle | Case-control study of risk factors for obstetric patients' admission to intensive care units[END_REF] reported a higher risk of maternal ICU admission among women with no antenatal care. This association may reflect the importance of regular ACU to screen for and treat some pathologies, such as severe pre-eclampsia.

The timing of initiation of ACU has been studied by Ayoola (39) who also found no association with neonatal ICU admission and very weak associations with preterm birth and low birth weight.

Nonetheless, we must point out three limitations to consider in interpreting the absence of an association between late initiation and severe morbidity in our study. Firstly, the threshold chosen to define late initiation is debatable and may be too early. Secondly, information on late initiation of care was collected postpartum, and we cannot rule out the risk of non-differential misclassification.

Thirdly, early interventions might have affected complications insufficiently represented in this study (fetal alcohol syndrome, congenital toxoplasmosis or rubella).

Our findings conflict with the results of a meta-analysis of randomised trials [START_REF] Bricker | Routine ultrasound in late pregnancy (after 24 weeks' gestation)[END_REF] assessing the effects of routine late pregnancy ultrasounds (after 24 weeks) that found no association between these examinations and perinatal mortality or preterm birth. Nevertheless, this meta-analysis has limitations.

It considered a relatively small number of studies, half of them took place in the 1980s at an early stage of utilisation of ultrasounds in antenatal care and the interventions and outcomes studied varied widely. Moreover, other studies found that antenatal diagnoses do affect perinatal mortality, [START_REF] Bonnet | Detection of Transposition of the Great Arteries in Fetuses Reduces Neonatal Morbidity and Mortality[END_REF][START_REF] Saari-Kemppainen | which considers the timing of initiation of care, percentage of recommended antenatal visits made, and ultrasound scans performed 543[END_REF] for example by improving the neonatal care of ultrasound-identified congenital malformations. Besides, our result cannot be explained by a higher rate of medical terminations among women with ultrasounds because terminations were included in SPM. Further research is needed to clarify the efficacy of routine ultrasounds in preventing SPM.

Other studies have reported an association between inadequate ACU, measured by ACU indexes, and perinatal morbidity (4-7). Most of them, however, took place in North America, where nearly twice as many visits are recommended than in France. Moreover, although we did find an association between a low rate of visits and SMM, the disappearance of this association when we used the mAPNCU index highlights the importance of the measures chosen and the possible disadvantages of using indexes.

Conclusion

Despite national policies supposed to guarantee universal access to antenatal care, a considerable proportion of women did not receive adequate antenatal care in our study. Those women are at higher risk of severely adverse maternal and perinatal outcomes, independent of their other characteristics.

More attention must be paid to women at risk of inadequate ACU, and interventions to improve ACU should be assessed.

Details of ethics approval:

  Association between inadequate antenatal care utilisation and severe perinatal and maternal morbidity: an analysis in the PreCARE cohort M Linard, B Blondel, C Estellat, C Deneux-Tharaux, D Luton, J. F. Oury, T Schmitz, L Mandelbrot, E Azria To cite this version: M Linard, B Blondel, C Estellat, C Deneux-Tharaux, D Luton, et al.. Association between inadequate antenatal care utilisation and severe perinatal and maternal morbidity: an analysis in the PreCARE cohort. BJOG: An International Journal of Obstetrics and Gynaecology, 2018, 125 (5), pp.587-595. 10.1111/1471-0528.14794. hal-03860693

Table 4 Association between antenatal care and severe maternal and perinatal morbidity

 4 The regional review board (CPP-Ile-de-France III, N° 09.341bis, date of approval: November 19, 2009) approved the study. Each woman provided oral informed consent, in compliance with French law.

	539
	Table 2 Antenatal care utilisation
		Prevalence
			N=9117
	Initiation of care	≥ 14 weeks n(%)	(17,0)
		< 14 weeks n(%)	(83,0)
	Number of scheduled antenatal visits	Mean (SD)	9,7	(3,4)
		Median (IQR)	(8-11)
	Percentage of recommended antenatal visits*	<50 n(%)		(2,6)
		50-79 n(%)		(9,6)
		80-109 n(%)	(38,5)
		≥110 n(%)	(49,4)
	First trimester ultrasound	No n(%)	(21,6)
		Yes n(%)	(78,4)
	Second trimester ultrasound	No n(%)	(16,8)
		Yes n(%)	(83,2)
	Third trimester ultrasound****	No n(%)	(16,2)
		Yes n(%)	(83,8)
	Antenatal care according to mAPNCU -1 index**	Inadequate n(%)	(18,5)
		Intermediate n(%)		(6,4)
		Adequate n(%)	(32,0)
		Adequate plus n(%)	(43,0)
	Antenatal care according to mAPNCU-2 index*** Inadequate n(%)	(34,6)
		Intermediate n(%)	(16,1)
		Adequate n(%)	(20,2)
		Adequate plus n(%)	(29,1)
	Abbreviations: weeks = weeks of gestation, mAPNCU = modified Adequacy of Prenatal Care
	Utilisation, SD = standard deviation, IQR = interquartile range
	* Percentage of recommended visits made, taking pregnancy duration into account
	** mAPNCU-1, which considers timing of initiation of care and percentage of recommended
	antenatal visits made
	*** mAPNCU-2, which considers initiation of care, percentage of recommended antenatal visits
	made, and ultrasound scans performed
	**** for pregnancies with delivery at or after 31 weeks of gestation
	540
	541

-2 index*** Inadequate 1,38 [1,06 ; 1,81] 1,37 [1,05 -1,80]

  Results of imputed models adjusted for maternal age, risk level at the beginning of pregnancy, body mass index, number of previous pregnancies, tobacco consumption, social deprivation, mother's place of birth, education level and maternity unit of delivery Abbreviations : OR = Odds ratio, aOR = Adjusted odds ratio, CI = Confidence interval, mAPNCU: modified Adequacy of Prenatal Care Utilisation index, weeks = weeks of gestation ¤ For pregnancies with deliveries at or after 31 weeks of gestation * Percentage of recommended visits made, taking pregnancy duration into account ** mAPNCU-1, which considers timing of initiation of care and percentage of recommended antenatal visits made

				1,11 [0,78 ; 1,58] 1,11 [0,77 -1,59]
	Intermediate	1,24 [0,90 ; 1,71]	1,25 [0,91 -1,73]	0,75 [0,47 ; 1,20] 0,79 [0,50 -1,24]
	Adequate	1	1	1	1
	Adequate plus	1,07 [0,80 ; 1,43]	1,07 [0,80 -1,42]	1,19 [0,83 ; 1,71] 1,13 [0,79 -1,63]

1

Acknowledgments:

The PreCARE cohort study was conceived by Professor Dominique Mahieu Caputo who worked intensely on this project until her premature death. The PreCARE study group wishes to pay tribute to this exceptional woman without whom this cohort would not have existed. The authors would like to thank Marion Schneider (URC Paris-Nord, APHP, Paris, France), Sofia Zemouri (URC Paris-Nord, APHP, Paris, France), Imane Younes (URC Paris-Nord, APHP, Paris, France), Nessima Yelles (URC Paris-Nord, APHP, Paris, France), Cosmina Husleag (URC Paris-Nord, APHP, Paris, France), Fadela Akroun (URC Paris-Nord, APHP, Paris, France), Lynda Lagha (URC Paris-Nord, APHP, Paris, France), Sarra Pochon (URC Paris-Nord, APHP, Paris, France), and the team of the CIC-EC 1425 for their help and support during this study..

Funding

This study was supported by grants from Medical Research Foundation (http://www.frm.org/), French Ministry of Health, PHRC 2007 and PHRC 2012 (http://www.sante.gouv.fr/le-programme-hospitalier-de-recherche-clinique-phrc.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.