1. Introduction
The prevalence of obesity has been increasing significantly in many countries in recent years [
1,
2]. For example, in the United States in 2008, 58.5% of reproductive age women are overweight or obese (body mass index ≥25 kg/m
2) [
3,
4] and the numbers are still increasing [
1,
2]. Pre-pregnancy body mass index (ppBMI), excessive and insufficient weight gain have been associated with adverse pregnancy outcomes, including small for gestational age (SGA), large for gestational age (LGA), macrosomia, caesarean delivery, gestational diabetes mellitus (GDM), preeclampsia, postpartum weight retention, and offspring obesity [
5,
6,
7,
8]. In 2009, the Institute of Medicine (IOM) updated its recommendations on gestational weight gain according to ppBMI [
9]. These guidelines were developed to minimize the negative health consequences for both mother and fetus of inadequate or excessive gain. They incorporated World Health Organization (WHO) categories of ppBMI maternal body mass index (BMI calculated as weight in kilograms divided by height in squared meters; BMI for underweight, <18.5; normal weight, 18.5–24.9; overweight, 25–29.9; and obese, ≥30) [
10], and recommended less gestational weight gain for obese women. A meta-analysis of over one million pregnant women highlighted that 47% had gestational weight gain greater than IOM recommendations, while 23% had gestational weight gain less than IOM recommendations, leaving only 30% of women considered with adequate gestational weight gain. Gestational weight gain above recommendations was associated with higher risk of LGA, macrosomia, and caesarean delivery [
11]. A retrospective study of chart abstractors from 29,861 women in 25 American hospitals found similar results with the addition of an association between gestational weight gain above the IOM recommendations and shoulder dystocia and neonatal hypoglycemia [
12].
In this context, we revisited the association of maternal pre-pregnancy weight and gestational weight gain with maternal and neonatal outcomes, taking advantage of a large prospective cohort of 7866 pregnant women recruited at their first prenatal visit to the perinatal clinic of the University Hospital in Quebec City, Canada. This clinic was the entry point for health care services for all pregnant women of the region. The important collection of data during the constitution of this cohort from an unselected low-risk population made it possible to evaluate IOM recommendations in the second and third trimesters of pregnancy, and to study the kinetics of weight gain using group-based trajectory modelling. This trajectory approach allows for an original study of the evolution of women’s weights during their pregnancies independent of the categories or recommendations of WHO or IOM.
4. Discussion
We studied the association of seven maternal and neonatal outcomes with ppBMI, IOM recommendations on gestational weight gain and weight gain trajectories during pregnancy. To our knowledge, we showed for the first time with an independent cohort, the relationship between IOM recommendations for gestational weight gain in the second trimester and perinatal outcomes. Furthermore, we showed that compliance with recommendations through both the second and third trimesters reduced the proportion of HDP, caesarean delivery, macrosomia, and LGA. Inversely, non-compliance with the recommendations between the second and third trimesters (i.e., going from within to above recommendations) increased the proportions of HDP, macrosomia and LGA. Finally, using group-based multi-trajectory modelling, we identified three profiles of pregnancy weight gain kinetics: profile A of women with normal ppBMI, profile B of rather overweight women with increased weight gain during pregnancy compared to the other two profiles and profile C of obese women. From profile A to profile C, the relative risk of GDM, HDP, caesarean delivery, macrosomia and LGA increased.
First, we validated our cohort by confirming that overweight and obese women show an increased relative risk of GDM, HDP, caesarean delivery and delivering a macrosomic or LGA neonate [
5,
25]. We also confirmed that underweight women are at increased relative risk of giving birth to SGA neonates and at decreased relative risk of caesarean, giving birth to a macrosomic or an LGA neonate [
5,
25]. Secondly, as demonstrated in two recent studies, including a meta-analysis [
11,
12], we validated our cohort by highlighting that in the third trimester of pregnancy, 13.3% of women were below IOM recommendations, while 53.8% were above IOM recommendations. Women with a gestational weight gain above IOM recommendations were at increased relative risk of HDP, caesarean, giving birth to a macrosomic or LGA neonate, and neonatal hypoglycemia.
With 53.8% of women above the IOM recommendations for gestational weight gain during pregnancy, it is questionable whether these are not too severe. However, it is noteworthy that those above IOM recommendations in the third trimester had a 1.92-fold increased risk of HDP, a 2.13-fold increased risk of macrosomia, a 2.28-fold increased risk of LGA and a 1.97-fold increased risk of neonatal hypoglycemia. Hyperinsulinism and insulin resistance caused by obesity and excessive weight gain [
26] may explain the increase in these risks [
27,
28,
29]. Our findings of the association of maternal and neonatal outcomes with IOM recommendations as early as the second trimester of pregnancy, and that compliance with recommendations between the second and third trimesters reduced this association, may have a significant impact on clinical practice. Indeed, these results should encourage physicians to confront pregnant women’s weight gain in the second trimester with IOM recommendations and to trigger appropriate interventions in cases of non-compliance. This is quite relevant considering that dietary and lifestyle interventions during pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Diet-based interventions are the most effective; they result in a reduction of maternal gestational weight gain and improve obstetric outcomes [
30]. IOM recommendations are thus relevant. Progress has been made on pregnancy weight gain control in the second trimester, but further efforts should be made in the third trimester. Indeed, we highlighted that 78.6% of women above the IOM recommendations in the second trimester of pregnancy remained above the recommendations in the third trimester. While we validated that obesity increases GDM risk by a factor of 3.9, it may seem surprising to note that GDM was more prevalent among women below IOM recommendations of gestational weight gain compared to those with normal weight gain. However, this has been previously observed [
12], and is probably attributed to a bias related to the treatment of women screened as diabetics and its potential effect on gestational weight gain. However, this may not explain the observed risk increase in the second trimester. This would need to be further studied.
Group-based multi-trajectory modelling allowed identifying three profiles of the kinetics of gestational weight gain independently of any recommendations. Using this approach, we identified three subgroups that clearly differed in ppBMI and gestational weight gain with a monotonic variation of the risk of the outcomes under study, including GDM. Obesity and particularly severe obesity (BMI >35 kg·m
−2) remain major risk factors of maternal and neonatal complications regardless of weight gain [
5], while the combination of pre-pregnancy overweight and increased weight gain during pregnancy represents an intermediate risk group.
An interventional study, triggering a medical intervention in patients with excessive weight gain according to IOM recommendations in the second trimester, would definitively confirm our results and the practical relevance of the IOM recommendations. The proportion of maternal and neonatal outcomes would be compared between an interventional group and a control group.
A strength of our prospective study was the homogeneity of our general population. With predominantly Caucasian (>98%) women and a public health system where all pregnant women have access to similar pregnancy follow up and monitoring, the possibility of sampling bias is reduced. With regards to socioeconomic aspects, the free access to perinatal care for the Quebec population may limit biases and contributes to generalizability of the results. However, the socioeconomic status had an effect on the perinatal outcomes even within a similar setting of universal access to health care [
31]. This is why we integrated the mother’s level of education and familial annual income in the adjustments of relative risks. Moreover, the homogenous origin of our cohort does not allow measuring the impact of ethnicity such as African origin. Women of African origin are more susceptible to being affected by obesity and excessive weight gain during pregnancy [
32]. Gestational weight gain recommendations specific for the Asian population are also necessary [
33]. Thus, external validity of our results should be tested in populations of different ethnic backgrounds. The lack of information on ppBMI or weight during pregnancy for 956 (12%) women of the cohort could be considered as a potential limitation. The exclusion of 956 (12.2%) women from the cohort due to the absence of information on ppBMI or weight during pregnancy may represent a selection bias. As explained above, the fact that some of the results confirm those of previous studies limits this bias [
34].