Pre-pregnancy maternal BMI as predictor of neonatal birth weight.

INTRODUCTION: BMI is a tool to measure maternal nutritional status. Maternal malnutrition is frequently reported health problem especially during child bearing age and effects neonatal birth weight. AIM: To determine relationship between prepregnancy maternal BMI and neonatal birth weight. METHODS AND MATERIAL: Prospective, cross sectional study conducted in Fatima Memorial Hospital, Lahore, Pakistan over a period of 1 year including 2766 mother-neonate pairs. All full term, live born neonates of both gender in early neonatal period (<72 hours) with documented maternal pre-pregnancy and/or first trimester BMI were enrolled. Data analysis using SPSS version 20, was performed.
RESULTS: Data analysis of 2766 mother-neonates pairs showed that there were 32.9% overweight and 16.5% obese mothers. More than two third of all overweight and obese mothers were of age group between 26-35 years. Diabetes mellitus, hypertension, medical illness, uterine malformations and caesarean mode of delivery were more prevalent in obese mothers as 22.8%, 10.1%, 13.2%, 2.6% and 75.4% respectively. Mean birth weight, length and OFC increased with increasing maternal BMI. Comparing for normal weight mothers, underweight mothers were at increased risk of low birth weight (p< 0.01) and low risk of macrosomic neonates (p<0.01). However overweight and obese mothers were comparable to normal weight mothers for delivering macrosomic neonates (p 0.89 and p 0.66 respectively).
CONCLUSIONS: Our study highlights that direct relationship exists between maternal BMI and neonatal birth weight.

Introduction

Maternal health status is a key determinant of foetal growth. Maternal malnutrition refers to deficiency, excess or imbalance in maternal intake of energy and/or nutrients [1]. Body mass index (BMI) is a globally accepted gauge to assess maternal nutritional status. It is calculated as weight in kilogram divided by the square of height in meter (kg/m2).

According to recommendations by Institute of Medicine (IOM) adapted by Pediatrics and Pregnancy Nutrition Surveillance System (PNSS), maternal BMI is classified as underweight (BMI <18.5), normal (BMI = 18.5 to 24.9), overweight (BMI ≥ 25.0 to 29.9) and obese (BMI ≥ 30) [2].

During childbearing age malnutrition, both under-nutrition, and obesity, is a global health problem. The developed countries share an increasing burden of overweight and obesity. Like in the USA, 4% of all American women are underweight, 47% normal, and 48% overweight [3]. Under-nutrition was once considered as a red flag in developing countries like in Pakistan. However, there is a change in trend and now Pakistan ranks among the top 10 countries where obesity is prevalent. About 23.9% and 6.3% of Pakistani females of childbearing age are overweight and obese respectively [4].

Maternal and fetal wellbeing is directly coupled. Optimal fetal growth is influenced by a number of factors. These factors through an intricate mechanism control fetal metabolic signaling pathways and guide “fetal programming”. Maternal nutritional status is most important among these factors as it ensures continuous nutrients supply to developing fetuses. Other factors are diabetes mellitus, hypertension, anemia, smoking, chronic illness, uterine problems, periodontal health, drugs, addiction, weight gain during pregnancy, parity, and the number of fetuses [5-7].

Growth assessment of neonate at birth is done by measuring weight, length, and occipitofrontal circumference (OFC) [8].

To author’s best knowledge, limited data of the Southeast Asian population in the context of IOM and PNSS guidelines for maternal BMI classification and neonatal birth weight is available. In particular, there is a paucity of studies conducted on Pakistani women. In a small study conducted in Islamabad, among 164 of total deliveries, 10% of low birth weight babies were born to mothers with BMI>25 [9]

The nutritional status of females in childbearing age, predicted by BMI, is a significant indicator of neonatal birth weight. Our study aimed to identify the relationship of maternal BMI with neonatal birth weight.

Material and methods

Study was conducted after ethical approval from IRB committee, Fatima Memorial Hospital, Lahore. Written Consent was taken from individual mothers for each mother-neonate pair in study.

This was a prospective, cross sectional study conducted in the Department of Neonatology, Fatima Memorial Hospital, Shadman Lahore, from November 2018 till October 2019. Data was screened for maternal-neonatal pairs.

Full term (born between 37+0 to 41+6 weeks complete gestation) live born neonates of both gender were enrolled in this study. All neonates were assessed for their growth parameters within 72 hours. Birth weight was measured using digital weight scale and categorized as low birth weight (< 2.5 kg), normal birth weight (2.5 to 4.0kg) and macrosmic (> 4.0kg) babies. Neonatal length and OFC were measured using infant-meter and OFC measuring tape respectively.

Maternal demographic data was collected from antenatal record documented on special hospital health card for each pregnant female. Only those mothers with documented maternal pre-pregnancy and/or first trimester BMI record were enrolled in this study. First trimester maternal weight was also acceptable as there is usually minimal weight gain during this period. We calculated maternal BMI as the main exposure and classified using Paediatrics and Pregnancy Nutrition Surveillance System (PNSS) as underweight (BMI <18.5), normal weight (BMI = 18.5 to 24.9), overweight (BMI ≥ 25.0 to 29.9) and obese (BMI ≥ 30).

The covariates maternal age, parity, gestational age, residence, mode of delivery (SVD–spontaneous vaginal delivery, instrumental or LSCS–low segment caesarean section), diabetes mellitus, hypertension, chronic medical illness, gestational weight gain, uterine malformation, poor periodontal health, anemia and blood transfusion, number of foetuses, drugs, addiction and smoking were addressed while calculating relationship between prepregnancy maternal BMI and neonatal birth weight.

WHO has defined optimal weight gain during pregnancy for each BMI group. For under weight it is 12 – 18kg, normal weight 11.5 – 16kg, over weight 7–11.5 kg and obese 5–9 kg [2]

All maternal–neonatal pairs were excluded with incomplete maternal or neonatal data, premature, neonatal age > 72 hours of life at first examination or refusal to participate.

Statistical analysis

All relevant data were recorded using a proforma in hand-writing and statistically analysed electronically using SPSS v20.

Maternal covariates for each BMI group were presented as descriptive statistics (numbers and percentages). Neonatal birth weight, length and OFC were presented as the means ± standard deviation for each maternal BMI group.

Multiple logistic regression model was used to correlate prepregnancy maternal BMI (primary exposure) and neonatal birth weight (primary outcome) while controlling all possible covariates / risk factors. Pairwise calculations were made for all BMI categories in form of mean difference and 95% confidence intervals (CI) while normal maternal BMI (18–24.9) was taken as reference category.

We performed analysis of variance (ANOVA) to test difference in mean birth weight for each maternal BMI group. Statistically significant difference among all BMI groups for mean birth weight was done by using Games-Howell post-hoc test and p-value less than 0.05 was taken as significant.

According to each maternal BMI group, descriptive statistics (number and frequency) was done for neonatal birth weight groups as low birth weight (<2.5kg), normal birth weight (2.5 – 4kg) and macrosmic (>4kg) babies.

Results

In present study 3390 mother—neonate pairs were enrolled initially but 624 were excluded (300 mothers were unaware of their pre-conceptional weight, 204 refused to participate in study, 75 mothers have incomplete data and 45 mother–neonatal pair presented after 72 hours of life).

Nearly 46.6% of the study population (n = 1290) included births to mothers with normal BMI. This was taken as the reference group to which other BMI groups were compared while using multivariate logistic regression. In the study population, 4.0% (n = 110) of the babies were born to mothers with underweight, 32.9% (n = 910) to overweight and 16.5% (n = 456) to obese mothers. Table 1 highlights the percentages and numbers of all mothers according to BMI categories for all covariates (maternal characteristics).

Table 1

Data of maternal characteristics according to BMI groups.

Maternal characteristics	Pre pregnancy maternal BMI kg/m2 n = 2766
	Underweight (BMI <18.5)	Normal weight (BMI 18.5 to 24.9)	Overweight (BMI ≥ 25.0 to 29.9)	Obese (BMI ≥ 30)	Total
	110 (4.0%)	1290 (47%)	910 (33%)	456 (16%)
Maternal age (years)
≤ 25	44(40.0%)	414 (32.1%)	186 (20.4%)	98 (21.5%)	742 (26.8%)
26–35	66 (60.0%)	806 (62.5%)	634 (69.7%)	330 (72.4%)	1836 (66.4%)
36–40	0 (0.0%)	70 (5.4%)	86 (9.5%)	28 (15.2%)	184 (6.7%)
>40	0 (0.0%)	0 (0.0%)	4 (0.4%)	0 (0.0%)	0 (0.1%)
Parity
Primiparous	32 (29.1%)	584 (45.3%)	318 (34.9%)	144 (31.6%)	1078 (39.0%)
2–5	78 (70.9%)	702 (54.4%)	592 (65.1%)	312 (68.4%)	1684 (60.9%)
>5	0 (0.0%)	4 (0.3%)	0 (0.0%)	0 (0.0%)	4 (0.1%)
Gestational age (weeks)
37–38	70 (63.6%)	758 (58.8%)	576 (63.3%)	314 (68.9%)	1718 (62.1%)
39–40	40 (36.4%)	510 (39.5%)	320 (35.2%)	140 (30.7%)	1010 (36.5%)
41–42	0 (0.0%)	22 (1.7%)	14 (1.5%)	2 (0.4%)	38 (1.4%)
Residence
Urban	110 (100.0%)	1210 (93.8%)	842 (92.5%)	422 (92.5%)	2584(93.4%)
Rural	0 (0.0%)	80 (6.2%)	68 (7.5%)	34 (7.5%)	12 (6.6%)
Mode of delivery
SVD	30 (27.3%)	322 (25.0%)	100 (11.0%)	70 (15.4%)	482 (17.4%)
Instrumental	6 (5.5%)	51 (4.0%)	105 (11.5%)	42 (9.2%)	176 (6.4%)
LSCS	74 (67.3%)	917 (71.1%)	705 (77.5%)	344 (75.4%)	2108 (76.2%)
Smoking	2 (1.8%)	6 (0.5%)	4 (0.4%)	0 (0%)	12 (0.4%)
Diabetes Mellitus	8 (7.3%)	122 (9.5%)	108 (11.9%)	104 (22.8%)	342 (12.4%)
Hypertension	0 (0)%	88 (6.8%)	202 (22.2%)	46 (10.1%)	336 (12.1%)
Medical illness	0 (0%)	114 (8.8%)	88 (9.7%)	60 (13.2%)	262 (9.5%)
Adequate weight gain during pregnancy	21 (19.1%)	184 (14.3%)	147 (16.2%)	89 (19.5%)	441 (15.9%)
Uterine malformation	0 (0%)	42 (3.3%)	24 (2.6%)	12 (2.6%)	78 (2.8%)
Periodontal health problems	44 (40.8%)	408 (31.6%)	268 (29.5%)	156 (34.2%)	876 (31.7%)
Drugs & addiction	0 (0%)	8 (0.6%)	24 (2.6%)	10 (2.2%)	42 (1.5%)
Anemia & blood transfusion during pregnancy	44 (40.8%)	418 (32.4%)	240 (26.4%)	150 (32.9%)	852 (30.8%)
Singleton pregnancy	94 (85.5%)	1252 (97.1%)	910 (100%)	440 (96.5%)	2696 (97.5%)

More than two third of all overweight and obese mothers were of age group between 26–35 years. Majority (93.4%) of study was consisted of urban population. Diabetes mellitus, hypertension, medical illness and uterine malformation were commonly documented in obese mothers as 22.8%, 10.1%, 13.2% and 2.6% respectively (Table 1). Periodontal health problems, anemia and blood transfusion during pregnancy were observed in both extremes of BMI (Table 1). Only 30.7% obese mothers completed full term gestation (39–40 weeks) as compared to 39.7% normal weight mothers (Table 1). The trend towards caesarean delivery with increasing BMI and noted to be 77.5% in overweight and 75.4% in obese mothers.

The results of multivariate linear regression analysis models, with birth weights as the dependent variables and the maternal BMI categories as the exposure variables controlling for study covariates, have been tabulated as Table 2.

Table 2

Pairwise comparisons of BMI groups for neonatal birth weights.

Neonatal birth weight	(I) Prepregnancy maternal BMI (18.5–24.9 (kg/m2)	(J) Prepregnancy maternal BMI (kg/m2)	p value	Mean Difference (I-J)	95% Confidence Interval for Difference b
					Lower Bound	Upper Bound
<2.5	ref	<18.5	0.96	.010	-.046	.067
		25–29.9	<0.01	-.081*	-.106	-.055
		≥ 30	<0.01	-.091*	-.122	-.060
>4	ref	<18.5	<0.01	-.045*	-.091	.000
		25–29.9	0.89	-.006	-.026	.014
		≥ 30	0.66	.004	-.021	.029
2.5–4	ref	<18.5	0.63	.035	-.035	.105
		25–29.9	<0.01	.087*	.056	.118
		≥ 30	<0.01	.088*	.049	.126

• Prepregnancy maternal BMI (18.5–24.9) is reference category.

• P-values obtained from Poisson regression models.

• Model was based on estimated marginal means significant (*) at p = 0.05.

• b Model adjusted for covariates maternal age, parity, gestational age, residence, mode of delivery, diabetes mellitus, hypertension, chronic medical illness, gestational weight gain, uterine malformation, poor periodontal health, anemia and blood transfusion, number of foetuses, drugs, addiction and smoking.

Our best esteem of difference show that both normal weight and underweight mothers are statistically equal for having low birth weight babies (p < 0.96, 95%CI -0. 046 to 0.067). However in overweight and obese mothers, incidence of low birth babies was low as compared to normal weight mothers (p < 0.01, 95%CI -0.106 to -0.055 and p < 0.01, 95%CI -0.122 to -0.060) respectively.

After adjusting for potential confounders, underweight mothers were less likely to have macrosomic neonates as compared to mothers with BMI 18.5–24.9 (p < 0.01, 95%CI -0.091 to 0.000). However there was no statistically significant difference between normal weight, overweight and obese mothers for prevalence of macrosomic neonates (p 0.89, 95%CI -0.026 to 0.014 and p 0.66, 95%CI -0.021 to 0.029) respectively.

Among all delivered neonates, there were 1468 male and 1298 female neonates. One-way analysis of variance (ANOVA) was conducted to evaluate the null hypothesis that maternal BMI has no effect on neonatal birth weight (n = 2766). The independent variable maternal BMI has 4 groups as underweight (M = 2.98, SD = 0.66, n = 110), normal weight (M = 3.13, SD = 0.62, n = 1290), overweight (M = 3.21, SD = 0.573, n = 910) and obese (M = 3.24, SD = 0.57, n = 456).

The assumption of normality was tenable to all 4 BMI groups. The assumption of homogeneity of variance was tested using Levene test and found not be tenable F (3, 2762) = 4.96, p = 0.002. However, robust tests of equality of means were found to be tenable by both Welch {F (3, 462.50) = 7.76, p = 0.000} and Brown- Forsythe {F (3, 634.39) = 7.86, p = 0.000}.

Post hoc comparison to evaluate pairwise difference among group means were conducted with the use of Games-Howell test since equal variance was not tenable. Test revealed significant pairwise difference in mean neonatal birth weight of undernourished and normal weight and overweight and obese mothers (p< 0.05).

However mothers with BMI <18.5 do not differ significantly from BMI = 18.5 to 24.9 (p>0.05). Similarly statistically insignificant difference was noted in overweight (BMI ≥ 25.0 to 29.9) and obese (BMI ≥ 30) (p>0.05).

Mean values of neonatal weight, OFC and length have been tabulated according to maternal BMI group in Table 3.

Table 3

Mean neonatal birth parameters according to maternal BMI groups.

Neonatal parameters	Maternal BMI (kg/m2) (n = 2766)
	<18.5	18.5–24.9	25–29.9	≥ 30
	(n = 110)	(1290)	(910)	(456)
Weight (kg)	2.99 ± 0.68	3.13 ± 0.62	3.21 ± 0.57	3.24 ± 0.57
Length (cm)	46.76 ± 2.93	47.92 ± 2.38	48.18 ± 2.38	48.53 ± 2.46
OFC (cm)	32.86 ± 1.2)	33.40 ± 1.2	33.37 ± 1.20	33.42 ± 1.30

According to each maternal BMI group, descriptive statistics (number and frequency) was done for neonatal birth weight groups as low birth weight (<2.5kg), normal birth weight (2.5 – 4kg) and macrosmic (>4kg) babies in Table 4.

Table 4

Descriptive statistics of neonatal birth weight groups according to maternal BMI.

Neonatal birth weight	Maternal BMI (kg/m2) n = 2766 (%age)
	<18.5	18.5–24.9	25–29.9	≥ 30	Total
<2.5	23 (20.9%)	184 (14.3%)	63 (6.9%)	27 (5.9%)	297 (10.7%)
2.5–4	86 (78.2%)	1034 (80.2%)	795 (87.4%)	401 (87.9%)	2316 (83.7%)
>4	1 (0.9%)	72 (5.6%)	52 (5.7%)	28 (6.1%)	153 (5.5%)

Discussion

Our retrospective cross-sectional study helped in determining the impact of maternal BMI on neonatal birth weight in a tertiary care hospital.

Dudenhausen JW et al found in their study that before pregnancy, 4% of all American women were underweight, 47% were normal, and 48% were overweight [3]. According to Calik et al, prepregnancy overweight and obesity was documented in 20.6% and 3.9% pregnant females respectively [10]. However studies conducted in Pakistan and Bangladesh have shown that there is a trend towards over weight (23.9% and 40.1%) and obesity (6.3% and 21.2%) respectively [4, 11]. Our study shows similar trend towards over weight and obesity. For every underweight mother, there were 8 overweight and 4 obese mothers. This increasing prevalence of BMI can be due to fact that all study population belonged to urban areas with easy access to health facilities. Also there are differences in their life style, eating habits and social-demographic profile. Moreover this study gives a clue of nutritional status of females according to new guidelines of PNSS (Pediatrics and Pregnancy Nutrition Surveillance System). To authors knowledge there are no such studies conducted in Pakistan following these parameters to actually determine BMI status.

There is global trend towards overweight and obesity with advancing maternal age >25 years [11-13]. Our findings support this trend. This alarming accelerated trend towards overweight and obesity is multifactorial including genetic, metabolic, advancing age and to add on sedentary life style and lack of healthy diet concept with use of lot of sugar, fats, processed and junk food [11, 14, 15].

Calik, Yazdani and Neumann have shown in their studies that 78.5%, 58.5% and 39.8% overweight and obese mothers were delivered by LSCS [10, 16, 17]. Similar trend toward caesarean delivery have been shown in our study. Large size baby and abnormal fat distribution have been well documented risk factor of caesarean delivery in over-weight and obese mothers [18, 19].

The Persian, Russian and Korean perinatal statistics have shown more prevalence of diabetes mellitus and hypertension in overweight and obese females [16, 19, 20]. With increasing BMI above normal, there is an increase in total body fat content that leads towards metabolic derangements leading to diabetes mellitus and hypertensive disorders in pregnancy [19].

Anemia and periodontal health issues are well reported perinatal health problems in both extremes of BMI [20, 21]. Mirror image results have been reflected in our study. This is due to lack of maternal knowledge of oral hygiene, healthy diet, food taboos and food selections. Moreover, there is usual trend of poor intake of iron, folic acid, calcium and vitamin D that worsens pre-existing anemia and periodontal health issues [22].

Maternal nutritional status has effect on foetal growth in terms of weight, occipito- frontal circumference (OFC) and length. Simko et al in their study have found that risk of large size baby increases in over weight and obese mothers as OR 11.7 (95%CI 1.2–2.3) and OR 1.8 (95%CI 1.2–2.7) respectively as compared to malnourished mothers OR 0.7 (95%CI 0.5–0.7) [21]. According to Moussa et al rate of large size babies increases linearly with increasing maternal BMI [23]. According to Gondwe et al, pre-pregnancy maternal underweight increased the risk of low birth weight babies; while overweight or obesity increased the risk of large size babies [24].

Our study shows that neonatal birth growth parameters are in direct relationship with prepregnancy maternal BMI. We documented significant differences in neonatal growth parameters among 4 BMI groups. In our study, mothers with BMI <18.5 had an inclination towards low birth weight neonates and their mean weight, OFC and length were lower as compared to other BMI groups. Macrosomic neonates were seen in mothers who were overweight and obesity in their prepregnancy period.

These mirror image results are due to fact that maternal and fetal wellbeing is directly coupled. The optimal maternal nutritional status ensures continuous nutrients supply to developing foetus for growth. Maternal wellbeing and optimal nutritional status through an intricate mechanism control fetal metabolic signaling pathways and guide “fetal programming” [5-7]. Both maternal over weight and obesity result in large size neonates due to alteration in foetal metabolic programming affecting hypothalamic-pituitary axis, pancreatic islet cells and adipose tissue [10, 25]. However malnourished mothers are at high risk of delivering a small sized baby and this is because of chronic nutritional deprivation status affecting foetal growth [19].

Conclusion

Studies determining the relationship of maternal BMI and neonatal birth weight are lacking in Pakistan. Our study highlights that there is a noteworthy direct relationship between maternal BMI and neonatal birth weight as low prepregnancy maternal BMI results in low birth weight neonates. However there is need of such more studies to highlight impact of such kind.

Study limitations

Our study had several limitations. First of all this study lacks external validity as vast majority of mothers were from urban area. Second, paternal demographic data as not entertained in this study which may influence neonatal growth parameters. Third, regarding maternal demographic data, we have to rely on information provided by mother as there is no national health registry system.

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23 Jul 2020

PONE-D-20-17353

Pre-Pregnancy Maternal BMI As Predictor Of Neonatal Birth Weight

PLOS ONE

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This manuscript has divided opinion amongst the reviewers. I believe that the study is not without interest but it is currently in need of a major revision before it could be considered for publication.

Even before considering the reviewers' comments, It is obvious that the manuscript requires major improvement in the quality of English language used. I would therefore suggest that the authors enlist the assistance of a native English speaker to help with this. I think that of the various reviewers' comments the most important to consider is that much of the study does not seem to relate directly to its stated aim. The paper needs to be written in such a way that it develops from its aim.  In addition, it is key to present the direct association between maternal BMI (as a continuous variable) and neonatal weight (also as a continuous variable) in any revision. Finally claims of "significance" need to be removed where p>=0.05 or the 95% confidence intervals cross either side of 1.00.

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Reviewer #1: I want to congratulate the authors for the effort in writing this interesting paper. Overall, I think the paper needs to improve the grammar and the fluency of the reading specially in the introduction section. I have other minor comments as well.

Introduction

- I'm not sure if maternal BMI measures body fat; instead, it is a ratio between weight and height, can you please include the reference of this sentence?

- It would be interesting to know the consequences of pre-pregnancy BMI on the offspring health

- Authors mention "fetal programming" but I would be interesting to know the conection between programming and pre-pregnancy BMI, at least in general.

- I'm not sure if the last sentence of the introduction section is related with the aim of the study, e.g. the study evaluates preventive measures?

Materials and methods

- Why authors did not consider materna weight gain during pregnancy as a newborn weight factor?

- I consider it is important to know the method to take the maternal measures as weight and height as well as the method to take the newborn weight.

- Why the authors did not include newborn height, not even as a characterisation variable?

- Medical records are electronic, hand writing, etc?

- How did the authors verifies the quality of data?

Results

- I don't understand the associations in table 1, I consider it need some legend at the end to clarify the comparisons between significant associations.

- City and village mean urbal and rural?

- As the main outcome is the birth weight, tables do not reflect that association. It seems like authors made associations with maternal BMI as the main outcome.

- I strongly recommend the authors to show the association between maternal BMI and birth weight, as it is the aim of the study.

Discussion

- It should be mainly about the association between birth weight and maternal BMI and not about the factors that affect maternal BMI

Reviewer #2: The results are not consistent with the purpose of the study. (Relation between pre-pregnancy BMI and neonatal birth weight, whereas majority of results concern on anemia, hypertension and diabetes mellitus).

Result are not statistically significant in many cases although authors state that they are.

In methods study is descripted as prospective, descriptive. In discussion study is descripted as retrospective, cross-sectional. It should be unified.

There is lack of information about excluded cases.

Table 1 show only that there is a lot of confounding factors, there is no possibility to form conclusion on it. There is lack of post-hoc tests. Authors made 2 categorizes of overweight and obese but then reported in as a one group >25kg/m2.

Table 2 is unclear. It related to risk factor of what in pregnancy? I can guess that it is risk factor of hypotrophy or macrosomia but I'm not sure. It should be explained what mean medical illnesses, uterine problems. I don't know why singleton pregnancy is a risk factor. According to WHO appropriate gestational weight gain is different for underweight, normal weight, overweight and obese. So 10-15 kg is not correct value.

The most important calculation which concern BMI and birth weight should be in table, no in graph without any statistics, not only in text. Also raw date about newborns length and occipital frontal circumferences give us no information.

In introduction there is a lot about malnutrition, but then authors conclude that in Pakistan there is much higher problem with overweight and obese, may be introduction should be rewritten.

Discussion is unclear, hard to read, not interesting.

There is lack of unit in BMI

There is lack of abbreviation explanation (SVD, LSCS, OFC)

**********

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Reviewer #1: Yes: Fanny Aldana-Parra

Reviewer #2: No

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16 Sep 2020

REBUTTAL LETTER

Date: Sep 06, 2020 21.00 pm

To: “PLOS ONE" plosone@plos.org"

From: Rafia Gul" docrafiagul@gmail.com

Subject: Response to reviewers

PONE-D-20-17353

Title: Pre-Pregnancy Maternal BMI as Predictor of Neonatal Birth Weight

Respected Petry and Reviewers,

It’s really an honor for me that your esteemed journal considered my article for review and highlighted things that required revision. Keeping in consideration your reviews, many changes have been made in article and have been highlighted as per your requirement.

COMMENTS:

Even before considering the reviewers' comments, It is obvious that the manuscript requires major improvement in the quality of English language used. I would therefore suggest that the authors enlist the assistance of a native English speaker to help with this. I think that of the various reviewers' comments the most important to consider is that much of the study does not seem to relate directly to its stated aim. The paper needs to be written in such a way that it develops from its aim. In addition, it is key to present the direct association between maternal BMI (as a continuous variable) and neonatal weight (also as a continuous variable) in any revision. Finally claims of "significance" need to be removed where p>=0.05 or the 95% confidence intervals cross either side of 1.00.

ANSWER:

• Quality of English has been improved with help of native English speaker to make it simpler and more understandable.

• Impact of maternal BMI on neonatal weight has been presented in more detail using statistical analysis

• Corrections in interpretation of statistically significant results have been done.

COMMENTS:

Please include the following items when submitting your revised manuscript:

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ANSWERS:

• A rebuttal letter has been attached under file name “ Response to Reviewers”

• A marked up copy that highlights changes made to original version labeled as 'Revised Manuscript with Track Changes'. has been uploaded

• An unmarked version of our revised paper without tracked changes labeled as “ Manuscript” has been uploaded

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

ANSWER:

No changes to your financial disclosure

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• Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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ANSWERS:

Not applicable

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ANSWER:

Manuscript has been organized according to PLOS ONE's style requirements

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

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We will update your Data Availability statement on your behalf to reflect the information you provide.

ANSWER:

Data for review has been made available

REVIEWERS' COMMENTS:

Reviewer's Responses to Questions

Reviewer #1:

COMMENTS:

I want to congratulate the authors for the effort in writing this interesting paper. Overall, I think the paper needs to improve the grammar and the fluency of the reading specially in the introduction section. I have other minor comments as well.

ANSWER:

Thank you so much for your kind response. I have tried to improve grammar and fluency to make it more understandable.

COMMENTS: Introduction

- I'm not sure if maternal BMI measures body fat; instead, it is a ratio between weight and height, can you please include the reference of this sentence?

- It would be interesting to know the consequences of pre-pregnancy BMI on the offspring health

- Authors mention "fetal programming" but I would be interesting to know the conection between programming and pre-pregnancy BMI, at least in general.

- I'm not sure if the last sentence of the introduction section is related with the aim of the study, e.g. the study evaluates preventive measures?

ANSWERS:

• BMI has been redefined in introduction

• Introductory part has been revised with addition of literature highlighting the consequences of pre-pregnancy BMI on the offspring health

• Concept of "fetal programming" has been eplined in more detail

• Aim of study has been rephrased.

COMMENTS: Materials and methods

- Why authors did not consider materna weight gain during pregnancy as a newborn weight factor?

- I consider it is important to know the method to take the maternal measures as weight and height as well as the method to take the newborn weight.

- Why the authors did not include newborn height, not even as a characterisation variable?

- Medical records are electronic, hand writing, etc?

- How did the authors verifies the quality of data?

ANSWERS:

• Maternal weight gain during pregnancy was part of original study. It had been mentioned as confounder factor of study.

• Methodology has been described in more detail regarding data collection format, measuring gadgets and persons involved.

• All neonatal birth parameters weight, length and OFC have been described in more detail.

COMMENTS : Results

- I don't understand the associations in table 1, I consider it need some legend at the end to clarify the comparisons between significant associations.

- City and village mean urbal and rural?

- As the main outcome is the birth weight, tables do not reflect that association. It seems like authors made associations with maternal BMI as the main outcome.

- I strongly recommend the authors to show the association between maternal BMI and birth weight, as it is the aim of the study.

ANSWER:

• Necessary changes have been made in table 1 to make more understandable

• Yes, city = urban , village = rural

• Impact of maternal BMI and neonatal birth weight has been statistically highlighted using ANOVA tests, post hoc analysis and multivariate regression analysis.

COMMENTS: Discussion

- It should be mainly about the association between birth weight and maternal BMI and not about the factors that affect maternal BMI

ANSWER:

Necessary changes have been made in discussion.

Reviewer #2:

COMMENTS:

1. The results are not consistent with the purpose of the study. (Relation between pre-pregnancy BMI and neonatal birth weight, whereas majority of results concern on anemia, hypertension and diabetes mellitus). Result are not statistically significant in many cases although authors state that they are.

2. In methods study is descripted as prospective, descriptive. In discussion study is descripted as retrospective, cross-sectional. It should be unified.

3. There is lack of information about excluded cases.

4. Table 1 show only that there is a lot of confounding factors, there is no possibility to form conclusion on it.

5. There is lack of post-hoc tests.

6. Authors made 2 categorizes of overweight and obese but then reported in as a one group >25kg/m2.

7. Table 2 is unclear. It related to risk factor of what in pregnancy? I can guess that it is risk factor of hypotrophy or macrosomia but I'm not sure. It should be explained what mean medical illnesses, uterine problems. I don't know why singleton pregnancy is a risk factor.

8. According to WHO appropriate gestational weight gain is different for underweight, normal weight, overweight and obese. So 10-15 kg is not correct value.

9. The most important calculation which concern BMI and birth weight should be in table, no in graph without any statistics, not only in text. Also raw date about newborns length and occipital frontal circumferences give us no information.

10. In introduction there is a lot about malnutrition, but then authors conclude that in Pakistan there is much higher problem with overweight and obese, may be introduction should be rewritten.

11. Discussion is unclear, hard to read, not interesting.

12. There is lack of unit in BMI

13. There is lack of abbreviation explanation (SVD, LSCS, OFC)

ANSWERS:

1. Results have been rationalized

2. Study design has been unified

3. Excluded cases have been described in more detail

4. Table 1 has been tabulated in better way

5. Post hoc test have been added

6. Overweight and obese mothers have been categorized and results for each group have been described for each group separately

7. Table 2 has been omitted for purpose of clearity

8. According to WHO appropriate gestational weight gain for each BMI group has been highlighted and results have been calculated accordingly.

9. Association of BMI and birth weight has been tabulated.

10. Introductory part has been rewritten with focus on overweight and obesity

11. BMI units as kg/m2 has been mentioned as per requirement

12. Abbreviations have been explained

Regards

Rafia Gul

2 Oct 2020

Pre-Pregnancy Maternal BMI As Predictor Of Neonatal Birth Weight

PONE-D-20-17353R1

Dear Dr. Gul,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Clive J Petry, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

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Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I consider the authors addressed the majority of my comments and the comments made by other reviewers, I consider that the paper can be published.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Fanny Aldana-Parra

8 Oct 2020

PONE-D-20-17353R1

Pre-pregnancy maternal BMI as predictor of neonatal birth weight

Dear Dr. Gul:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Clive J Petry

Academic Editor

PLOS ONE