The impact of abnormal maternal body mass index during pregnancy on perinatal outcomes: a registry-based study from Qatar

Objectives: Abnormal body mass index (BMI) during pregnancy, a growing public health concern, increases maternal and neonatal complications. This study aimed to investigate the impact of abnormal BMI on perinatal outcomes compared to normal BMI. Methods: A total of 14,624 women having singleton births were categorized as underweight (BMI<18.5 kg/m 2 ), overweight (25.0 – 29.9 kg/m 2 ), obesity class I (30.0 – 34.9 kg/m 2 ), obesity class II (35.0 – 39.9 kg/m 2 ), and obesity class III ( ≥ 40.0 kg/m 2 ) and comparedtothosewithnormalBMI(18.5 – 24.9 kg/m 2 ).Outcomes included gestational diabetes (GDM), gestational hypertension (GHT), postpartum haemorrhage (PPH), cesarean delivery (CD), preterm birth (PTB), low birth weight (LBW), congenital anomalies and neonatal intensive care unit admission. Results: Women with increasing BMI had increasingly higher odds of developing speci ﬁ c adverse outcomes, the highest being in the class III obesity group (GDM-aOR 2.71, 95 % CI 2.25 – 3.27, p<0.001, GHT-aOR 5.32 95 % CI 3.49 – 8.11, p<0.001, CD-aOR 2.33 95 % CI 1.85 – 2.94, p<0.001, PPH-aOR 1.77 95 % CI 1


Introduction
The World Health Organization (WHO) states that obesity, described as harmful excessive body fat, is one of the most significant global health issues of the twenty-first century due to the alarming rise in prevalence, which has tripled since 1975.By 2030, it is estimated that 1 in 5 women and 1 in 7 men will be living with obesity, which equates to more than 1 billion people worldwide [1][2][3].The most widely used biomarker of obesity is body mass index (BMI), obtained by the weight in kilos divided by the square of the height in meters.The WHO categorizes BMI into four groups based on the increasing risks for conditions such as diabetes, heart disease, and cancer leading to premature death [4].Along with the rise in obesity rates in the general population, obesity during pregnancy has increased, making it a common high-risk condition in obstetrics today [5].Approximately 38.9 million pregnant women worldwide were overweight or obese in 2021 [6].
Following the global alert for overweight and obesity, attention has been directed to the other extreme of nutritional status in developing and developed countries [9].Less research has been targeted at the effect of maternal underweight, that is associated with adverse neonatal outcomes [10].Although GHT, preeclampsia, and GDM are less likely to occur in women with low BMI, these women have higher risks of preterm delivery, fetal intrauterine growth restriction (IUGR), and small for gestational age (SGA) [11,12].
Due to recent changes in social and cultural factors, diet and nutrition, lack of physical activity, and rapid urbanization, there is an expanding concern with quickly growing obesity and its linked medical problems in the Middle East [13].In Qatar, adult obesity was 40.0 % in men and 49.7 % in women in 2014.However, there is a lack of research in Qatar that quantifies the adverse effects of abnormal BMI on pregnancy, which would help develop targeted management strategies.This study aimed to evaluate the association between abnormal maternal BMI (underweight, overweight, and obesity) and adverse maternal and neonatal outcomes among singleton pregnancies compared to normal maternal BMI.

Study design and setting
This registry-based study included women delivering at the largest tertiary maternity hospital in Qatar (averaging 16-18,000 deliveries per year) between January 2017 and December 2017.The data used in this study was extracted from the PEARL Peristat registry (Perinatal Neonatal Outcomes Research Study in the Arabian Gulf), a populationbased registry funded by the Qatar National Research Fund (Grant number NPRP 6-238-3-059), including maternal and fetal outcomes of all hospital deliveries during the registry period.Additional ethical approval specific for this study was not required, as only secondary analysis of registry data was done.

Participants
We extracted data from women with a reported live birth after singleton pregnancies, gestational age (GA)≥24 completed weeks at birth, and a BMI documented at the first antenatal visit.The women were categorized into five exposure groups based on WHO BMI classification: underweight (BMI<18.5 kg/m 2 ), overweight (BMI 25.0-29.9kg/m 2 ), obesity class-I (BMI 30.0-34.9 kg/m 2 ), obesity class-II (BMI 35.0-39.9kg/m 2 ), and obesity class-III (BMI≥40.0kg/m 2 ).Women with a normal BMI (18.5-24.9kg/m 2 ) formed the comparison group (unexposed).Those with a booking BMI in the first trimester were analyzed separately to explore the antenatal weight gain in the different BMI groups.

Data source and variables
The maternal demographic variables included: -Maternal age: in years-continuous variable; and categorized into two groups, median age used as the cutoff.-Nationality as documented in official hospital records: classified into Qatari and non-Qatari.-Parity-defined as previous births at ≥24 weeks gestation.This variable was classified into three groups-nulliparous (no previous births), multiparous (1-3), grand multiparous (≥4).-Number of previous CDs-classified into two groups (0 previous CD and ≥1 previous CD).-Pre-existing medical illnesses such as diabetes, chronic hypertension and anaemia (yes/no).
Maternal age and parity were considered apriori confounders and were adjusted for in the analysis of all outcomes.Other known confounders were also adjusted for, provided they did not fall in the causal pathway between maternal BMI and the outcome variables.
The primary maternal and fetal outcome variables included: -Gestational diabetes (GDM)-defined as an abnormal 75 g glucose tolerance test performed between 16 and 32 weeks gestation according to the prior risk of the patient.-Gestational hypertension (GHT) -first onset of hypertension occurring after 20 weeks of gestation [14] (including preeclampsia and eclampsia) in women not known to have chronic hypertension.-Mode of delivery-vaginal delivery (spontaneous and instrumental) vs. CD (elective and emergency).-Postpartum haemorrhage (PPH)abnormal bleeding after birth (>500 mL during vaginal delivery and >1000 mL during CD [15].-Preterm birth (PTB)-defined as delivery before 37 completed weeks of gestation [16].-Low birth weight (LBW)-birthweight<2,500 g, regardless of gestational age at birth [17].-Macrosomia -birthweight>4,000 g, regardless of gestational age at birth [18].-Admission to NICU-baby requiring admission to intensive care unit after birth for any reason.-APGAR score of <7 at 1 min of life-as evaluated by the delivery midwife or the attending neonatologist.-Congenital anomalies-any internal or external physical anomalies at birth diagnosed by the attending neonatologist after clinical examination and/or imaging.
Additionally, for women who had their first antenatal visit in the first trimester (≤13 completed weeks), the maternal gestational weight gain (GWG) was calculated as the difference between the documented maternal weight in kilograms at booking and delivery.This variable was classified into three categories depending on if the weight gain observed during pregnancy was less than the lower limit, within or more than the upper limit of the expected range of weight gain in pregnancy for each BMI group, as sourced from the Institute of Medicine international guidelines for weight gain in pregnancy [19].

Statistical methods
Continuous variables were reported as mean ± standard deviation (SD) or median ± interquartile range (IQR) according to the distribution of the variable (assessed by histograms and Shapiro Wilk test for normality) and compared using one-way ANOVA or Kruskal-Wallis test as appropriate.Categorical variables were described using frequencies and percentages and compared using Chi-Square or Fisher's exact test as appropriate.
The frequencies of each outcome variable were calculated, and the percentages of the total in each group were depicted as bar graphs to visualize the differences between the groups.Adjusted odds ratios (aOR) and 95 % confidence intervals (CI) were calculated using multivariable logistic regression models, adjusting for confounders.The normal BMI group formed the baseline group for calculating the ORs.The weight gain during the antenatal period was reported as mean ± SD.
All statistical analysis was performed in STATA statistical software, Release 16 [20].The null hypothesis for the models stated that there is no difference in the odds of outcomes in each abnormal BMI group compared to the normal BMI group.A p-value <0.05 provided evidence against this null hypothesis and was considered statistically significant.
The maternal demographics in the different exposure groups are shown in Table 1.As the BMI increased, a higher proportion of women were older (≥30 years age group).Nearly 70 % in the obesity-III group belonged to the older age group compared to only 16 % in the underweight category.A higher proportion of women in the class-II and class-III groups were Qatari.Grand multiparity was more prevalent as the BMI increased, with around 20 % and more multiparous women in the three obesity groups.In addition, 50 % of mothers in the underweight group were nulliparous.
More than 30 % of women in the obesity groups had a previous CD (38 % in obesity-III) compared to only 7 % in the underweight group.Women in the overweight and obesity groups had a higher prevalence of pre-existing diabetes and chronic hypertension compared to other groups, with an increasing trend noted as the BMI increased.Nearly 16 % of women in the underweight category suffered from anaemia, compared to nearly 10 % in the overweight and obesity groups.

Maternal outcomes
An increasing trend was noted in the incidence of the various maternal outcomes as the BMI groups moved from underweight to class-III (Figure 1).The risk of GDM in this cohort was 30 % (4,212 out of 14,255 women without preexisting diabetes).Nearly 44 % of women in the highest BMI group developed GDM compared to 20 % in the underweight    Similarly, the odds of developing GHT increased steadily from an aOR of 1.60 (95 % CI=1.14-2.24,p<0.001) in the overweight group to an aOR of 5.32 (95 % CI=3.49-8.1,p<0.001) in class-III group.In the last two groups, the odds of CD delivery were nearly twice that of the control group (aOR=1.96,95 % CI=1.66-2.31 and aOR=2.33,95 % CI=11.85-2.94respectively, p<0.00).The odds of PPH were 25-30 % higher in the overweight and class-I groups, which increased to 77 % higher odds in class-III (aOR 1.77, 95 % CI 1.35-2.33).The model for PPH excluded the women with missing data for blood loss at the time of delivery (n=107, 0.7 %).
The underweight category had similar chances of GDM and CD compared to the control.For GHT, a 21 % reduction in odds was seen (aOR=0.7995 % CI=0.19-3.29),and a 38 % reduction for PPH (aOR=0.62,95 % CI=0.33-1.15)were noted in this group.However, none of these associations reached statistical significance (p>0.05).

Neonatal outcomes
There was an 8 % incidence of PTB and LBW babies in our sample, which increased sharply to 14 % PTB and 16 % LBW in the underweight group while remaining roughly similar in all other groups (Figure 2).Similarly, in the cohort with a 1.5 % risk of congenital anomalies, the underweight group had more than double the risk (3.5 %).The incidence pattern of macrosomia had the familiar upward slant with the increase in BMI, with the highest risk (9 %) noted in the highest BMI group.Nearly 11 % of the babies were admitted to the NICU, which rose to 14-15 % in the extreme BMI groups (underweight and class-III).More than 2 % of the babies had a low APGAR at 1 min of life, roughly the same in all exposure groups.
Women in the underweight group had 2.52 times higher odds of an infant with congenital anomalies (95 % CI=1.12-5.64,p=0.025).The other BMI groups had similar odds to the control group.Additionally, there were higher odds of admission to NICU in the extreme BMI groups-50 % higher odds (aOR=1.49,95 % CI=0.99-2.24)and 36 % higher odds (aOR=1.36,95 % CI=1.04-1.77) in the underweight and class-III groups respectively.There were 20-30 % lesser odds of low APGAR score at birth in the underweight, overweight and class-I groups; however, these associations did not reach statistical significance.

Gestational weight gain
There were 4,796 women with a booking BMI recorded in the first trimester.The mean GWG was 11.1 ± 4.7 kg in the underweight group, 10.7 ± 5.4 kg for women with normal BMI, 9.3 ± 5.9 kg for overweight women, and 7.9 ± 6.4 kg, 6.2 ± 5.8 kg, and 5.2 ± 6.3 kg for classes I, II and III respectively  (Table 4).These values were compared to the expected GWG.Only 30 % of our cohort had a GWG within the expected range for each BMI group.Nearly 67 % in the underweight group had less than average expected weight gain, compared to the 56 % in the normal BMI group and 45-46 % in the class II and III groups.In class-I, 42 % of women gained more than expected (highest among all groups).

Discussion
The study results unequivocally show that belonging to the underweight, overweight or obesity categories increases the probability of unfavourable maternal and neonatal outcomes.The odds of developing maternal outcomes such as GDM, GHT, PPH, and delivery by CD and neonatal outcomes such as macrosomia were higher with increasing BMI categories compared to the normal BMI group, with no difference detected between the underweight and normal BMI group.On the other hand, women in the underweight group had a higher chance of PTB, LBW, and congenital anomalies.Both extremes of BMI categories had higher odds of NICU admission.By classifying women according to their BMI, this study specifically demonstrates a link between increasing BMI (from overweight to obesity class-III) and increased risk of adverse outcomes.Our results are consistent with previous studies showing an association between abnormal BMI and poor maternal and neonatal outcomes [21].Similar findings from a case-control study conducted in Tehran revealed that obese mothers had a 4.5-fold higher risk of developing hypertensive diseases in pregnancy [22].In the US, as the mother's BMI increased compared to normal, the prevalence of cesarean deliveries increased by 28.3 % [23].
In our study, maternal BMI was found to significantly affect birthweight, with women with obesity more likely to have macrosomic babies and women in the underweight category more likely to deliver babies with LBW.This conclusion is reinforced by a meta-analysis reporting that obese women had a 2-fold higher risk of giving birth to a macrosomic baby [24].In a study conducted in India, mothers underweight during pregnancy had a 17.2 % risk of LBW babies, similar to our study [25].This high rate of LBW infants is concerning due to the increased risk of infant mortality and morbidity [26].
Our study shows a 2.5 times higher odds of congenital anomalies in babies born to underweight women, supported by Mezzasalma et al. [27], who reported a higher incidence of anomalies like the nervous system, orofacial and urogenital anomalies [27].Meta-analyses report that maternal obesity, not maternal underweight, is significantly linked to an increased risk of congenital heart disease in their offspring.Metabolic changes such as elevated estrogen levels, hyperinsulinemia, high blood pressure, high blood sugar, and nutritional deficiencies may make women with obesity more vulnerable to having babies with congenital anomalies [28].
Another study investigating the association of maternal pre-pregnancy BMI with infant mortality showed that newborns with spina bifida born to underweight or obese mothers had poorer chances of survival than newborns of mothers with normal weight [29].However, our study does not demonstrate a statistically significant association between obese women and congenital anomalies in their babies.This could be because this study looks at congenital anomalies as a whole and not any specific anomaly leading to a lack of power in detecting this association.
Based on results from observational studies looking at associations between GWG and preterm birth, small and large for gestational age at birth, CD, postpartum weight retention, and childhood obesity, the US Institute of Medicine (IOM) published revised recommended gestational weight gain ranges in 2009.These ranges are 12.5-18 kg, 11.5-16 kg, 7-11.5 kg, and 5-9 kg for underweight, normal weight and obese women, respectively [30].
Our results show that a significant proportion (nearly 70 %) of women in the underweight category did not achieve the expected weight gain.A 2021 study conducted in India showed a 44 % higher risk for LBW in women gaining below the expected GWG [31].This could explain the higher incidence of LBW noted in our study in the underweight group.Only 22 % of class-III women gained more than expected GWG in our cohort; however, this group still had the highest incidence of GDM, GHT, and CD.In addition, studies investigating the influence of GWG on the health of newborns among class-III women report a higher incidence of admission to NICU [32], which is similar to the results in our study regardless of the GWG in that group.This emphasizes the importance of adequate preconception weight and nutrition management, as the BMI at conception appears to have a more considerable impact on the outcomes than the GWG alone.
According to Vesco et al., gaining below IOM recommendations protected against large for gestational age babies but increased the risk for SGA [33].Similarly, the study by Bloomberg in 2011 found that class-III women faced a higher likelihood of SGA when losing weight while having more favourable maternal outcomes [34].However, more than half of the class-III in our study gained more than the recommended weight during their pregnancy; hence the outcomes in this group contrast with the studies mentioned.
The overall findings of our study highlight the importance of addressing abnormal BMI in pregnant women, as it can have significant implications for maternal and neonatal health.Additionally, these results suggest that interventions to prevent and manage abnormal BMI in women of reproductive age may positively impact maternal and neonatal outcomes.The findings of this study can help change clinical practice, such as improving preconception counselling starting from an early age and setting up dedicated antenatal abnormal BMI clinics to manage pregnancies with abnormally high or low maternal BMI.This is particularly important given the increasing rates of obesity in Qatar and globally.Further interventional studies can prove the impact of these interventions on perinatal outcomes.

Strengths and limitations
To our knowledge, this is the first study in Qatar and the Middle East region to examine each distinct category of BMI, including the underweight group and pregnancy outcomes.One of the study's key strengths is standardized classifications which makes it possible to make valid comparisons with other studies and include these results in meta-analyses.In addition, the women in the study represent the pregnant population in Qatar, as more than 80 % of deliveries in the country occurs at the study site.Qatar has a heterogenous population consisting of women from nearly 100 different nationalities, which differs from more homogenous populations in other countries.Therefore, results from this local study will be much more relevant to inform changes in clinical practice in Qatar.
This study has the advantage of using registry data extracted meticulously by trained data collectors.Missing data, if present, were<1 % of the total number and therefore did not affect the analysis or interpretation.The large numbers make the study well-powered to detect important differences in the chosen outcomes.There was an apriori consideration of possible confounders, and adjusted models were used to determine associations, excluding variables in the causal pathway.This gives more strength and credibility to the associations noted.
However, some limitations must be considered while interpreting the results.The study results apply to only women satisfying the inclusion criteria.Pregnancies less than 24 weeks, with multiple pregnancies and those complicated by intrauterine fetal death, were excluded, leading to a small underestimation of the prevalence of outcomes such as GDM, GHT, and CDs.Misclassification of the exposure groups is possible due to human error in entering the height and weight in the medical records-however, this is unlikely to vary according to any outcome.Many women choose not to perform a glucose tolerance test and hence might not be diagnosed-this is more likely in women in the underweight or normal BMI groups leading to an underestimation of the incidence of GDM in these groups.Finally, residual confounding is still a concern as there is significant heterogeneity in the pregnant population of Qatar and various socioeconomic factors impacting pregnancy outcomes that are difficult to adjust for.

Conclusions
In conclusion, this study highlights the need for healthcare providers to be aware of potential risks associated with abnormal BMI.Belonging to the overweight or obesity categories during pregnancy negatively influenced maternal and neonatal outcomes with a rising risk as BMI increases.Since obesity is becoming more common among women of reproductive age, it is expected that the burden of maternal obesity will increase further in the future.Therefore, it is crucial to utilize resources wisely when planning antenatal care for women with abnormal BMI to minimize perinatal complications and undue burden on healthcare.

Figure 1 :
Figure 1: Percentages of women in each group with maternal pregnancy outcomes.

Table  :
Distribution of maternal demographic variables among the exposure groups.
normal BMI groups.Similarly, 8 % of women in the class-III group developed GHT compared to 1-1.5 % in the lowest BMI groups, the overall risk in our study sample being 3 %.The risk of CD in the normal BMI group was 22 %.While this risk decreased in the underweight group, the risk steadily increased as the BMI increased and more than doubled (47 %) in the class-III group.In addition, with a 10 % risk of PPH in the entire cohort, there was a steady increase in the incidence from 8 % in the normal BMI group to a maximum of 13 % in the highest BMI group.Women in the overweight group had 40 % higher odds of developing GDM (aOR=1.40,95%CI=0.26-1.55,p<0.001), as shown in Table2.Furthermore, the OR increased steadily with BMI and class-III group had 2.71 times higher odds of developing GDM (aOR=2.71,95 % CI=2.25-3.27,p<0.001).
a Compared using ANOVA, Continuous variables represented as mean ± standard deviation.Categorical variables analysed using Chi-Square test; p<. considered evidence again null hypothesis of no difference.The bold values were used to highlight all the percentages as it is a crowded table and we intended the focus to be on the percentages, however this is not necessary to be done.and

Table  :
Adjusted odds ratios for the association between BMI categories and neonatal outcomes.
Preterm birth adjusted for age and parity categories, nationality, pre-existing diabetes, and chronic hypertension.Low birth weight adjusted for age and parity categories, nationality, pre-existing diabetes, and chronic hypertension ( missing data).Macrosomia adjusted for age and parity categories, nationality, pre-existing diabetes, and chronic hypertension ( missing data).Admission to NICU and APGAR score < adjusted for age and parity categories, chronic hypertension, and pre-existing diabetes.Congenital anomalies adjusted for age and parity categories, nationality, chronic hypertension and pre-existing diabetes.a =p<.strong evidence against null hypothesis of no difference.The bold values represent all the statistically significant results at the cut off of p<..

Table  :
Gestational weight gain in women with first-trimester booking.