Keywords
cesarean section - diabetes gestational - fetal macrosomia - obesity - high-risk pregnancy
Descritores
cesariana - diabetes gestacional - macrossomia fetal - obesidade - gravidez de alto
risco
Introduction
The World Health Organization (WHO) considers obesity a worldwide epidemic and one
of the greatest public health challenges of the 21st century. According to the WHO, in 2016, across Europe, 24.5% of women aged ≥ 18 years
old were obese.[1] In the same year, in Portugal, the prevalence was 21.2% and represented a 3-fold
rise since 1975 (6.8%).[2]
[3]
The etiology of obesity is multifactorial and complex. Obesity is related to genetic
predisposition, physiological changes to the endocrine system of the body, potential
genetic contributions over generations, cultural beliefs, and socioeconomic issues.[4]
Obesity has a major impact on both morbidity and mortality. Obesity is a risk factor
for type 2 diabetes mellitus (DM), hypertension, dyslipidemia, and coronary heart
disease. Also, obesity decreases quality of life because of associated mood disorders,
such as anxiety and depression, and aggravated osteoarticular complaints.[4]
[5]
In pregnancy, obesity is a risk factor for adverse maternal, obstetrical, and fetal/neonatal
outcomes, contributing to prolonged hospitalization periods, both for the mother and
the baby.[4]
[6] Obesity increases risks of venous thromboembolism, gestational diabetes, preeclampsia,
dysfunctional labor, cesarean delivery, postpartum hemorrhage, wound infection, miscarriage,
fetal/neonatal death, and abnormal fetal growth, either macrosomia or growth restriction.[7]
[8] Moreover, children of obese parents have a two to three times higher risk of becoming
obese adults. It seems that the in utero environment plays a causative role in this vicious cycle.[4]
Obesity in pregnancy is defined as a body mass index (BMI) equal to or greater than
30 Kg/m2 at the first prenatal visit. It is further subclassified in: class I (30.0–34.9 Kg/m2), class II (35.0–39.9 Kg/m2), and class III (≥ 40 Kg/m2).[8]
The aim of the present study was to understand to what extent obesity is related to
adverse maternal, obstetrical, and neonatal outcomes in a Portuguese obstetrical population.
Methods
Study Design
This retrospective case-control study was conducted using 4 years of data of women
who gave birth at the Department of Obstetrics of a differentiated perinatal care
University Hospital, between January 2013 and December 2016. Only singleton pregnancies
were considered. Ethics approval was obtained from the Ethics Committee of our hospital.
A total of 9,371 participants were selected. Information about BMI at the first prenatal
visit was lacking from 659 medical records and these pregnant women were promptly
excluded. The remaining 8,712 pregnant women were categorized according to WHO BMI
categories, based on the registered weight at the first prenatal visit.[8] Overweight women (n = 2,130) were further excluded to get a more accurate comparison, because overweight
pregnant women are predisposed to obesity. The final analysis included 6,582 singleton
pregnancies: A group of 1,183 obese pregnant women (cases) were compared with a group
of 5,399 normal or underweight pregnant women (controls) for maternal, obstetrical,
and neonatal outcomes.
Data Collection
Maternal, obstetrical, and perinatal data from singleton pregnant women who gave birth
in the maternity facility, irrespective of type of pregnancy follow-up, were collected
from Obscare (Virtual Care, System for life, Porto, Portugal), an institutional medical
record software for obstetricians and pediatricians.
Variables Description
Information was collected on women's age, parity, weight (at the first and last prenatal
visits), and BMI (Kg/m2) at the first prenatal visit. The weight gain was calculated from the difference
in weight between the last and first prenatal visits and used as a continuous variable.
Gestational diabetes was diagnosed according to the International Association of the
Diabetes and Pregnancy Study Groups criteria (IADPSGC).[9] Hypertensive pregnancy disorders (gestational hypertension and preeclampsia) were
considered when maternal blood pressure was ≥ 140 mm Hg (systolic) or ≥ 90 mm Hg (diastolic)
on two occasions, at least 4 hours apart, after 20 weeks of gestation, in a woman
with a previously normal blood pressure.[10] Other variables studied were delivery mode, fetal demise, gestational age at birth,
birth weight, Apgar score, neonatal intensive care unit admission, and neonatal death.
Preterm birth was classified as extreme preterm (24–28 weeks), very preterm (29–32
weeks), and moderate/late preterm (32–36 weeks). After this categorization of preterm
birth, it has also been grouped to be estimated as a dichotomous variable – preterm
and term births. An updated and validated Portuguese birthweight chart was used to
obtain birthweight percentiles.[11] Newborns were classified as small for gestational age (SGA) when birth weight was < 10th percentile for the gestational age, and as large for gestational age (LGA) when the
birth weight was ≥ 90th percentile. Low birthweight was considered when infants weighed ≤ 2,500 g, and macrosomia
when they weighed ≥ 4,000 g. Gestational diabetes, hypertensive pregnancy disorders,
delivery mode, fetal demise, neonatal intensive care unit admission, and neonatal
death were evaluated as dichotomous variables.
Blood glucose values, in the first (fasting) and second (fasting, 1 and 2 hours after
75 g glucose load) trimesters of pregnancy were evaluated and compared between groups,
as continuous variables.
Statistical Analysis
Descriptive statistics were performed for demographic, clinical, and laboratory data.
Mean and standard deviation (SD) were calculated for normally distributed variables.
For group comparisons, parametric (t test student and analysis of variance [ANOVA]),
and nonparametric tests (Mann-Whitney test) were used, as appropriate, for continuous
variables, and the Pearson Chi[2] test for categorical variables.
Logistic or linear regression analysis, as appropriate, for univariate and multivariate
models were used for each of the outcomes. Odds ratio (OR) was adjusted for age, number
of gestations, parity, weight gain, hypertensive pregnancy disorders, and gestational
diabetes. All of the results were considered significant if the p-value was < 0.05. Statistical analyses were performed using Stata version 12.1 (Stata Corp,
College Station, TX, USA).
Results
The prevalence of obesity in the obstetrical population studied, as registered in
the first prenatal visit, was 13.6%, and the mean BMI was 24.7 Kg/m2 ([Table 1]).
Table 1
Distribution of pregnant women by body mass index category
|
BMI category (Kg/m2)
|
Number (prevalence %)
|
|
Underweight (< 18.5)
|
325 (3.7)
|
|
Normal weight (18.5–24.9)
|
5074 (58.2)
|
|
Overweight (25.0–29.9)
|
2130 (24.5)
|
|
Obesity
|
1183 (13.6)
|
|
Obesity class I (30.0–34.9)
|
819 (9.4)
|
|
Obesity class II (35.0–39.9)
|
268 (3.1)
|
|
Obesity class III (≥40)
|
96 (1.1)
|
Abbreviation: BMI, body mass index.
[Table 2] summarizes maternal characteristics. The obese group of women was significantly
older, more frequently multiparous, and gained less weight during pregnancy than normal
or underweight women.
Table 2
Maternal characteristics
|
Obesity group (n = 1,183)
|
Control group (n = 5,399)
|
OR
|
p-value
|
|
Age (years old) (mean, SD)
|
31.5 (5.5)
|
30.7 (5.6)
|
–
|
< 0.001
|
|
Age > 35 years old (%)
|
32
|
26
|
1.37 (1.2–1.57)
|
< 0.001
|
|
Number of gestations (n‡)
|
2.1
|
1.8
|
–
|
< 0.001
|
|
Nulliparous (%)
|
35
|
47.5
|
0.59
|
< 0.001
|
|
BMI (kg/m2) (mean, SD)
|
34.1 (3.9)
|
21.7 (4.9)
|
–
|
< 0.001
|
|
Weight gain (kg) (mean, SD)
|
10.5 (6.8)
|
14.3 (4.9)
|
–
|
< 0.001
|
Abbreviations: BMI: body mass index; kg: kilograms; n: number; OR: odds ratio; SD:
standard deviation.
Obese women had a significantly higher prevalence of gestational diabetes (17.6% versus
5.5%, adjusted odds ratio [aOR] 2.14; 95% confidence interval [CI]: 1.53–3.00) and
hypertensive pregnancy disorders (9.0% versus. 2.6%, aOR 3.43; 95%CI: 2.33–5.12).
Concerning the mode of delivery, the cesarean section rate was significantly more
frequent in the obesity group compared with the control group (35.3% versus 24.4%).
After adjusting for confounders, obese pregnant women had twice the odds of delivering
by cesarean (aOR 2.0; 95%CI: 1.64–2.47) compared with normal or underweight women.
The difference was even more significant among primigravidae (aOR 2.27; 95%CI: 1.65–3.11).
No differences were found in preterm birth rates between the 2 groups (8.3% versus
7.1%, obesity and control groups respectively, p = 0.17). The mean birth weight was significantly higher in the obese group (3,226 ± 531 g)
compared with the control group (3,132 ± 506 g). Large for gestational age and macrosomic
newborns were significantly more prevalent among obese women (12.8% versus 6.9%, aOR
2.13; 95%CI: 1.54–2.96; and 6.4% versus 3.2%, aOR 2.94, 95%CI: 1.95–4.45, respectively),
even when adjusted for age, parity, weight gain, gestational diabetes, and hypertension.
Considering the morbidly obese pregnant women (BMI ≥ 40 Kg/m2), the risk of having a macrosomic newborn was > 9 times higher than that of a normal
or underweight pregnant woman (aOR 9.5; 95%CI: 3.7–24.6) ([Table 3]). In contrast, obese pregnant women had significantly fewer SGA newborns (9.7% versus.
12.1%, p = 0.009), but no statistical significant difference was observed for the low birthweight
variable.
Table 3
Risks of maternal, obstetrical and neonatal outcomes according to obesity class
|
Control
|
Obesity class I
|
Obesity class II
|
Obesity class III
|
|
aOR
|
aOR (95%CI)
|
aOR (95%CI)
|
aOR (95%CI)
|
|
Gestational diabetes
|
Ref
|
1.98 (1.35–2.9)
|
2.42 (1.37–4.26)
|
2.1 (0.92–4.80)
|
|
Hypertensive pregnancy disorders
|
Ref
|
3.52 (2.27–5.45)
|
2.54 (1.10–5.85)
|
6.38 (2.49–16.35)
|
|
Cesarean section
|
Ref
|
1.78 (1.41–2.25)
|
2.61 (1.77–3.85)
|
3.19 (1.79–5.71)
|
|
SGA
|
Ref
|
0.59 (0.41–0.84)
|
0.62 (0.35–1.10)
|
0.1 (0.02–0.50)
|
|
Low-birthweight infant
|
Ref
|
0.71 (0.49–1.03)
|
0.45 (0.24–0.85)
|
0.08 (0.20–0.38)
|
|
LGA
|
Ref
|
1.69 (1.17–2.44)
|
3.93 (2.36–6.60)
|
7.0 (3.42–14.30)
|
|
Macrosomia
|
Ref
|
2.25 (1.35–3.74)
|
5.02 (2.47–10.20)
|
9.53 (3.70–24.60)
|
Abbreviations: aOR, adjusted odds ratio; LGA, Large for gestational age; Ref, reference
value; SGA, Small for gestational age.
All variables are adjusted for age, number of gestations, parity, weight gain, hypertensive
pregnancy disorders, gestational diabetes.
According to a local institutional policy, immediate postpartum umbilical cord blood
gas analysis is performed only in cases of suspected fetal hypoxia/acidosis. In a
total of 4,388 tests, fetal acidemia (pH < 7.2 in umbilical artery) was more frequently
found in the obese group of women (8.9% versus 6.7%, p = 0.008), but no differences were found among the groups for severe acidemia (pH < 7.05
in the umbilical artery). Apgar score < 7 at 5 minutes was identical in both groups
(1.2%, p = 0.95), and even though more newborns from obese women were admitted to the neonatal
intensive care unit (ICU), the difference was not statistically significant (6.8 versus
5.6%, p = 0.23).
Fetal and neonatal death rates were not significantly different between obese pregnant
women (n = 4, 0.3%) compared with the normal or underweight pregnant woman (n = 32, 0.6%).
[Table 3] presents maternal, obstetrical, and neonatal outcomes according to obesity class.
The risk of gestational diabetes, hypertensive pregnancy disorders, cesarean delivery,
LGA, and macrosomic infants increased with increasing BMI class. In contrast, the
odds of low birth weight and SGA infants decreased with increasing BMI class.
Blood glucose levels were significantly higher for obese pregnant women compared with
normal or underweight women (p < 0.001) ([Table 4]). Also, mean blood glucose levels were found to progressively increase with increasing
class of obesity ([Table 5]).
Table 4
Blood glucose levels (mg/dL)
|
Obesity group (mean, SD§)
|
Control group (mean, SD)
|
p-value
|
|
1st trimester fasting
|
83.5 (9.0)
|
79.3 (7.2)
|
< 0.001
|
|
2nd trimester fasting
|
77.8 (9.4)
|
73.8 (17.4)
|
< 0.001
|
|
2nd trimester 1-hour after OGTT[¶]
|
127.6 (31.3)
|
113.9 (29.3)
|
< 0.001
|
|
2nd trimester 2 hours after OGTT[¶]
|
109 (26.6)
|
98.6 (24.9)
|
< 0.001
|
Abbreviation: SD, standard deviation.
¶ OGTT (oral tolerance glucose test), 75 gr glucose load (fasting, 1 and 2 hours after),
at 24–28 weeks.
Table 5
Blood glucose levels (mg/dL) according to obesity class
|
Control (χ ± SD[‡])
|
Obesity class I (χ ± SD)
|
Obesity class II (χ ± SD[‡])
|
Obesity class III (χ ± SD)
|
p-value (ANOVA)
|
|
1st trimester fasting
|
79.3 (7.2)
|
82.5 (8.6)
|
85.5 (10.1)
|
86.1 (8.5)
|
< 0.001
|
|
2nd trimester fasting
|
73.8 (17.4)
|
77.5 (9.8)
|
77.9 (8.1)
|
80.0 (7.5)
|
< 0.001
|
|
2nd trimester 1-hour after OGTT[†]
|
113.9 (29.3)
|
127 (32.2)
|
128.1 (28.5)
|
132.2 (28.7)
|
< 0.001
|
|
2nd trimester 2 hours after OGTT[†]
|
98.6 (24.9)
|
108.8 (29.9)
|
109.8 (27.3)
|
109.1 (22.1)
|
< 0.001
|
Abbreviations: ANOVA, .Analysis of variances model; SD, standard deviation.
† OGTT (oral tolerance glucose test), 75 gr glucose load (fasting, 1 and 2 hours after),
at 24–28 weeks.
‡ χ: mean.
Discussion
Our study reported a 13.6% prevalence of maternal obesity in a Portuguese population
of 6,582 singleton pregnancies. So far, this information concerning specifically a
Portuguese obstetrical population was unavailable.
Obese pregnant women included in the analysis were significantly older and more frequently
multiparous than normal or underweight women, reflecting a progressive tendency for
weight gain with increasing age and parity.[12]
Excessive weight gain during pregnancy is a hallmark of poor metabolic control and
favors adverse pregnancy outcomes.[7]
[8] The 2013 American College of Obstetricians and Gynecologists (ACOG)[13] recommendations for weight gain during pregnancy for obese women was between 5 and
9.1 Kg. In our study, the average weight gain during pregnancy in obese women exceeded
the maximum allowed (10.5 Kg). This finding should alert Portuguese physicians involved
in women's and antenatal medical care to specifically address prevention and management
of obesity, through nutritional changes, physical conditioning, and promotion of healthy
lifestyle changes.
The results from the present study support the fact that maternal obesity is a major
risk factor for adverse pregnancy and perinatal outcomes.
We demonstrated that gestational diabetes is twice as likely for obese pregnant women,
which is somewhat lower than the odds reported in the literature (OR 3.6–7.5).[7]
[14] We also demonstrated increases in mean blood glucose levels, during the first and
second trimesters of pregnancy, with increasing BMI class. The HAPO study explained
this metabolic change through increases in insulin resistance with higher BMI values
and suggested that gestational diabetes and obesity seem to share common metabolic
features, such as increased insulin resistance, hyperglycemia, and hyperinsulinemia.[15]
Hypertensive pregnancy complications were also more likely to occur in obese pregnant
women and, specifically, in the morbidly obese pregnant women (BMI > 40 Kg/m2) (aOR 6.38; 95%CI: 2.49–16.35) ([Table 3]). Analogously, an Australian study demonstrated that obese pregnant women had 3
times the odds of having a hypertensive disorder during pregnancy, and the risk was
even higher among the morbidly obese (OR 4.87; 95% CI: 3.27–7.24).[12]
In our study, maternal obesity was an independent risk factor for delivering macrosomic
and LGA infants. In contrast, maternal obesity reduced the risk of SGA or low birthweight
newborns.[16]
Cesarean delivery rates have been increasing over the past 30 years in both developed
and developing countries. In Portugal, by the year 2011, cesarean sections accounted
for 35% of total deliveries.[17] These high rates led to the creation, in 2013, of a National Committee for Safe
Motherhood and Newborn Health to try to counteract this tendency toward an unnatural
way of birth.[18] In accordance with the published literature, our study demonstrated a negative influence
of maternal obesity on delivery mode, favoring cesarean section ([Table 3]).[7]
[19]
[20] Obese pregnant women were two times more likely to have cesarean sections compared
with normal or underweight women, and the odds were three times higher for the morbidly
obese. This difference persisted even when considering only primigravidae, which excluded
the effect caused by obstetric history, such as cesarean section. So, the increase
in maternal obesity further contributes to the present difficulty in achieving the
2015 WHO's goal for a cesarean section rate of 10 to 15%.[17]
In the literature, there is controversy regarding the association between maternal
obesity and preterm birth.[7]
[12]
[16] Our study found similar rates of preterm birth for both obese and normal or underweight
women.
Our study did not demonstrate increased rates of fetal or neonatal death in the obese
group of women, which is different from what is already published.[7]
[8]
[16] This result may be explained by the number of obese women, which may have been insufficient
to evaluate infrequent adverse obstetrical and neonatal events such as fetal or neonatal
death.
The present study has further limitations. First, the present findings were derived
from a single maternity hospital in Portugal, so that, despite the large sample, limited
generalization is possible. Also, the study is a retrospective comparative analysis
of maternal, obstetrical, and neonatal data, and some data could not be collected.
For example, in an unknown percentage of medical records, maternal weight, as registered
in the first prenatal visit, may not have been objectively measured, leading to self-reported
errors concerning this important variable.[16]
This is the first Portuguese study that specifically addressed maternal, obstetrical,
and neonatal outcomes in a population of singleton obese pregnant women and compared
them with those of normal or underweight pregnant women.
Conclusion
In accordance with the published literature, the present retrospective case-control
study was able to demonstrate that obesity is associated with increased odds of adverse
pregnancy and neonatal outcomes, such as gestational diabetes, hypertensive pregnancy
disorders, cesarean section, macrosomia, and LGA newborns. Moreover, the occurrence
of adverse outcomes increased progressively with increasing BMI class. To conclude,
the results of our study reinforce the fact that it is imperative to consider female
obesity as a major public health issue and to take measures to prevent and treat this
condition, specifically among woman of childbearing age.
