Antepartum maternal weight indices, Maternal Serum Leptin and Birth Weight: A cross-sectional comparative study

doi:10.21203/rs.3.rs-5277802/v1

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Antepartum maternal weight indices, Maternal Serum Leptin and Birth Weight: A cross-sectional comparative study

https://doi.org/10.21203/rs.3.rs-5277802/v1

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Background: Obesity has adverse effects on pregnancy outcomes, including macrosomia. Both have adverse synergistic effects on each other.

Aim and Objectives: To determine the association between Maternal weight, BMI, and birth weight.

Methods: This was a cross-sectional comparative study carried out over months. The case (experiment) group included neonates with macrosomia and their mothers. The control group was neonates with normal birth weight and their mothers. The maternal weight, height and body mass index were measured at booking and before delivery and categorized using the WHO obesity classification. The Data was analyzed using Stata statistical package version 14. Continuous variables, including age, birth weight, and mean leptin levels, were summarized by mean± standard deviation. There was a test of associations between variables to determine a significant relationship at a p-value of < 0.05. A total of 45 mother-neonate pairs that completed the study were used in the analysis. The study participants include 23 mother -neonate pair with normal weight and 22 mother-neonate pair with macrosomia. The mean birth weight was 3.78±0.05. The mean age of the women was 29.93±5.32, with the 25-29 age group being the modal age group. Only 2(9.09%) out of the 22 women with macrosomia had normal BMI at booking. There was a significant relationship between WHO Obesity class at booking and macrosomia (p-value=0.03). The mean maternal weight at delivery was 88.93±15.28. There was a significant association between the mean maternal weight before delivery and birth weight (83.17 for normal weight and 94.95±12.42 for macrosomia) p-value=0.004. The mean maternal serum leptin was 4.90±1.82. The value was higher but not statistically significant in women that gave birth to macrosomic babies.

Conclusion: Maternal prenatal weight indices showed a significant association with macrosomia. As recommended by the World Health Organisation, pregnant women should be counselled on the need for proper weight gain during pregnancy and interventions should be instituted to make sure they achieve appropriate weight gain. Early booking should also be encouraged for proper counselling, dietary interventions and follow up.

Maternal booking weight

maternal weight before delivery

BMI

Macrosomia

Fetal macrosomia is a neonate with a birth weight of 4 kg or more, regardless of gestational age and is associated with complications during delivery. These include shoulder dystocia, birth injuries, increased operative deliveries and birth trauma to the mother. (1–3)

Fetal macrosomia is an independent risk factor for developing obesity in adulthood. It may be a potential target for halting the obesity scourge and fetal reprogramming through the identification of methods of fetal reprogramming. Macrosomic neonates and low birth weight are at increased risk of hypertension and hypertriglyceridemia. (4,5)

The prevalence of macrosomia is highly variable. It affects about 3–15% of all deliveries. (6) While the incidence is higher in developed countries, rising prevalence has been documented in developing countries. Najafian and Cheraghi et al. (7) reported a prevalence of 9% in a cohort of women in Iran, while Ezegwui et al. reported 8.1% in Nigeria. (8) A multicenter study by Koyanagi et al. (1) reported 7.9% in Nigeria and 14.9% in Algeria using 4.0kg as the cutoff.

Increasing evidence supports the hypothesis that fetal development is influenced by maternal and fetal factors that determine the intrauterine environment; the adaptation of the fetus to this environment results in fetal "programming". (9,10) Fetal nutrition, stress and environmental toxins will alter cell numbers and nutrition. The result of the alteration will be altered gene expression and function. (Excessive gestational weight gain may induce a persisting susceptibility to obesogenic environment during childhood (and later during adulthood).

Maternal obesity and weight gain in pregnancy affect fetal weight and neonatal body composition. Greater maternal BMI among adult women increases the risk for enlarged birth size, greater neonatal fat mass and overweight/obesity during childhood. (11,12) Whisner et al. observed that maternal diet but not gestational weight gain predicts central fetal adiposity. (13)

Pederson hypothesized that maternal hyperglycemia is mainly responsible for fetal macrosomia (the maternal hyperglycemia-fetal hyperinsulinemia hypothesis. (14) Maternal hyperglycemia increases glucose supply to the growing fetus through the utero-placenta unit. The increased uptake of glucose and subsequent storage increases fetal adiposity, while the insulin-like growth factors act as growth factors.

Pederson's hypothesis cannot explain the macrosomia seen in non-diabetic women. This implies that there are other factors responsible for macrosomia. Soprano et al., in their study, observed that being macrosomic at birth is an independent risk factor for childhood overweight and obesity. (15)

World Health Organization (WHO) has classified obesity in pregnancy using pre-pregnancy body mass index (BMI) to calculate the appropriate gain for each class for pregnant women. This is aimed at reducing the impact of obesity on pregnancy outcomes.

The role of leptin as an intrauterine growth modulator has been a subject of controversy. A conflicting report about the relationship between maternal serum leptin and birth weight exists. (16,17) This calls for further studies to determine the exact relationship between fetal growth and birth weight.

A periodic review of the rate and effects of maternal weight on birth outcomes is needed. This will help identify the problem's magnitude and priority areas in intervention and research. The study evaluated the relationship between maternal weight at booking before delivery, serum maternal leptin and birth weight.

The study was a cross-sectional analytical study carried out over five months. The control group were neonates with normal birth weight and their mothers. The normal birth weight was defined as a birth weight between 2.50 to 3.99kg. The case (experiment) group included neonates with macrosomia and their mothers. Macrosomia was defined as a birth weight equal to or greater than 4.0kg.

The study was conducted at a tertiary health institution, Nnamdi Azikiwe University Teaching Hospital (NAUTH) in Nnewi, Nigeria. The neonates with normal weight and their mothers were the control group. Babies with macrosomia and their mothers were the experiment group.

Inclusion criteria include Informed consent, term singleton pregnancy

Exclusion criteria: included neonates with congenital anomalies, birth weight lower than 2.5kg, and known cases of diabetes in pregnancy.

The sample size was calculated using the formula (Charan and Biswas 2013) for comparative studies, assuming a power of 80% and standard deviation of 0.7019(the mean of the birth weight in a previous survey = 0.701(2), ratio 1: 1 for experiment and control group, standard normal variation for level of significance at 1% type 1 error = 2.58, mean difference between the control (normal birth weight) and case (macrosomia in a previous study) = 1.0(18)

Assuming an attrition rate of 15% (errors in estimated weight, congenital anomalies and other exclusion criteria, samples that will spill and those that may give indeterminate results),

n = 21 for each group and a total of 42. The subjects were stratified into two arms. The first arm was the experiment group, while the second arm was the control. For each subject recruited into the experiment group, a control was recruited and matched for parity and gestational age that meets the inclusion criteria. Each day, the folders of expectant mothers who arrived at the antenatal clinic at 37 completed weeks were carefully reviewed to identify those who met the inclusion criteria and were utilized to identify potential patients at term. The folders were coded to avoid double recruitment.

These women received extensive counselling during the study. An ultrasound was utilized to identify the pregnant woman at term based on the estimated fetal weight. Utilizing ultrasonographic measures of the biparietal diameter (BPD), abdominal circumference (AC), and femur length, the fetal weight was determined using the Hadlock 3 formula (FL). Participants were enlisted for the study at the antenatal clinic. About 5mls of blood were taken from each to estimate the mother's leptin level. Both the height and weight of the participants were measured before delivery. The booking weight was measured at the first antennal visit. The booking BMI and the BMI before delivery were calculated using the formula Weight divided by height squared. The BMI was classified using the WHO classification of obesity.

Birth weight was measured within 2 hours of delivery using an identical neonatal weighing scale (SECA, China). Two readings of naked weight were obtained, and the average reading was recorded. Placenta weight was also measured after inspection.

HUMAN LEPTIN ASSAY METHODOLOGY

Serum or plasma total leptin was measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit for human leptin manufactured by Biovendor® (Biovendor- Laboratornimedicinaa.s, Karasek 176 7/1, 62100. Brno/Zech Republic)

5.8 DATA ANALYSIS

The statistical program STATA 14 was used to analyze the data. Leptin levels, birth weight, and other continuous variables such as age were summarized by mean and standard deviation. A test of associations was conducted to identify significant relationships between variables with a p-value of less than 0.05. The relationship between maternal weight, BMI and birth weight was determined using paired student test. The maternal leptin and birth weight were displayed on a two-way scatter diagram using Pearson's correlation coefficient.

Before the study started, ethical permission was obtained. The study was conducted according to Helsinki's principle.

A total of 45 mother-neonate pairs that completed the study were used in the analysis. This comprises 23 mother -neonate pair with normal weight and 22 mother-neonate pair with macrosomia. The mean age of the women was 29.93 ± 5.32, with 25–29 age groups being the modal age group. The mean gestational age was 21.89 ± 7.90 weeks. None of the sociodemographic parameters were significantly associated with birth weight. This is shown in Table 1

Table 1

Sociodmographic Parameters of the participants
Parameter	Birth Weight		X²	p-value
	Macrosomia	Normal weight
Maternal age
< 20	1 (4.5)	0
20–24	3 (13.6)	4 (17.4)
25–29	8 (36.4)	8 (34.8)	1.2121	1.000
30–34	5 (22.7)	5 (21.7)
≥ 35	5 (22.7)	6 (26.1)
Marital status
Married	20 (90.9)	22 (95.6)
Single	1 (4.5)	0	1.073	0.739
Divorced	1 (4.5)	1 (4.4)
Highest Educational Attainment
Tertiary	14 (63.6)	13 (56.5)	0.237	0.626
Secondary	8 (36.4)	10 (43.5)
Occupation
Artisan	3 (13.6)	3(13.04)
Civil servants	8(36.36)	8 (34.78)
Housewife	2 (9.09)	2 (8.70)
Student	5 (22.73)	4 (17.39)
Trader	3 (13.64)	6 (26.09)

The mean birth weight was 3.78kg ± 0.05. The mean maternal weight at booking was 79.97kg ± 14.94. This was significantly higher among women with macrosomic neonates with a p-value of 0.02 (75.50kg in normal weight versus 84.64kg among women with macrosomia). The maternal BMI at booking was also significantly higher in women with macrosomic neonates with a p-value of 0.04(26.95 in the normal birth weight group compared to 29.41 in the macrosomia group). The mean maternal weight before delivery was 88.93kg ± 15.28. There was a significant association between the mean maternal weight before delivery and birth weight (83.17kg for the normal weight group and 94.95kg ± 12.42 for the Macrosomia group), p-value = 0.004. The mean BMI before delivery was 31.32. This was significantly higher among women with macrosomia, with a p-value of 0.01( 29.74kg for the normal weight group versus 32.96 in the Macrosomia group).

The mean maternal serum leptin was 4.90 ± 1.82. The value is higher but not statistically significant in women that gave birth to macrosomic babies ( 4.68 in the normal weight group versus 5.12 in Macrosomia group). Table 2 shows the mean weight at booking, mean BMI at booking, BMI before delivery, maternal weight before delivery, and mean serum maternal leptin in Macrosomia neonates and normal-weight neonates.

Table 2

Mean maternal serum leptin, Maternal weight before delivery, maternal BMI before delivery, Booking weight, maternal BMI at booking and birth weight.
Variable	mean ± std (95%CI)	normal (95%CI)	macrosomia (95%CI)	t- test	p-value
Birth Weight	3.78 ± 0.50	3.38 ± 0.36	4.2 ± 0.18	9.362	< 0.001*
Mean Maternal Weight at Delivery	88.93 ± 15.28 (84.34–93.52)	83.17 ± 15.77 (76.3589.99)	94.95 ± 12.42 (89.44-100.46)	2.76	0.004*
Mean BMI at delivery	31.31 ± 4.67 (29.91–32.72)	29.74 ± 4.9 (27.60-31.89)	32.96 ± 3.79 (31.28–34.64	2.43	0.01*
Mean Booking weight	79..97*14.94 (75.48–84.46)	75.50 ± 16.39 (68.41–82.58)	84.64 ± 11.91 (79.36–89.92)	2.13	0.02*
Booking BMI	28.16 ± 4.71 (26.74–29.57)	26.95 ± 5.09 (24.75–29.16)	29.41 ± 4.00 (27.64–31.18)	1.79	0.04*
Mean Maternal Leptin	4.90 ± 1.82	4.68 ± 1.83	5.12 ± 2.05	0.79	0.22
BMI = Body mass index
*=significant

According to the WHO classification, only 13(28.89%) of the women were in the normal weight category. Thirty-two(72.11%) were either overweight or obese. The overweight and Obese groups each contributed 16(35.56%). None of the participants was either underweight or morbidly obese at booking. There was a significant relationship between WHO Obesity class at booking and macrosomia (p-value = 0.016). The relationship between WHO obesity classification and macrosomia is shown in Table 3.

Table 3

WHO OBESITY CLASSIFICATION AT BOOKING AND BIRTH WEIGHT
BMI	normal n(%)	macrosomia n(%)	TOtal n(%)	p-value
UNDERWEIGHT (BMI < 19)	0	0	0	0.016
NORMAL (BMII 19-24.9)	11(47.83)	2(9.09)	13(28.89)
OVERWEIGHT (BMI 25-29.9)	7(30.43)	9(40.91)	16(35.56)
OBESITY CLASS 1 (BMI 30-34.9)	3(13.04)	9(40.91)	12(26.67)
OBESSITY CLASS 2 (BMI 35-39-9)	2(8.70)	2(9.09)	4(8.89)
OBESITY CLASS 3 (BMI > = 40)	0	0	0
TOTAL	23	22	45

Figure 1: Scatter Diagram showing Correlation between Mean Maternal Serum Leptin level and Birth weight (r = 0.258, p-value = 0.087)

Mean age and gestational age were not statistically different among the two groups. This is not surprising because of the nature of the study, which matched both arms. Previous studies observed that age and gestational age were significantly associated with macrosomia. (19)

Mean maternal weight at booking and before delivery, mean maternal BMI at booking and before delivery had a significant association with delivery of a Macrosomia neonate. Our observation is comparable to a report by Pereda et al. that noted excessive maternal weight gain; overweight and obesity at the end of pregnancy are independent risk factors for fetal macrosomia. (20) This is in keeping with work by Gaudet et al., that also observed that obesity is an independent risk factor for fetal macrosomia in a systemic review and meta-analysis. (21)

Our finding also agrees with observations by Jolly et al. that obesity leads to more macrosomia cases than diabetes mellitus because it is commoner. (22) Said and Manji in Tanzania (18) and Kamanu et al. in Nigeria (23) observed that maternal weight greater than 80kg is a risk factor for macrosomia which is in keeping with our observation.

The relationship between macrosomia and the mean maternal leptin level was not statistically different. This is in line with the findings in another study. (17) This supports the observation that maternal leptin's role in-utero is still unclear.

We observed that most women were in the obese or overweight category at booking. Thus these calls for preconception care to provide counselling, education and lifestyle modifications for would-be pregnant women to help them achieve optimal pre-pregnancy weight, booking weight and gestational weight gain. The mean gestational age at booking of 22 weeks means the women do not book early. The preconception care and antepartum counselling will help to encourage them on the need for early booking.

The findings in our study imply that any long-term plan to reduce macrosomia should involve modifiable factors, including weight reduction, especially before and during pregnancy. Healthy living including appropriate food and exercise should be encouraged. Caution should also be exercised to ensure these measures do not lead to starvation. More researches is needed in areas of maternal nutrition.

Macrosomia and obesity have adverse synergistic effects on each other. While obesity is an independent risk factor for macrosomia, the latter is also a risk factor for obesity. Thus, controlling and reduction of obesity in pregnant women will not only lead reduction of macrosomia, it will also modify the effects of in-utero programming, which predisposes the offspring of obese women to obesity and all the attendant metabolic complications in childhood and adulthood. Hence, we infer that proactive and deliberate measures should be instituted at national, regional and local levels to reduce the burden of obesity by targeting its disruptive effects on fetuses in utero and neonates after delivery through education, including exercise and proper diet preconception, during the pregnancy period and beyond.

One of the strengths of this study is that we matched cases of macrosomia and normal birth weight thereby reducing the bias associated with the outcome variables. We also categorized the BMI using the WHO obesity classification. One of the limitations of the study is that it is a single-centre study. Therefore, the generalization should be done with caution.

Maternal antenatal weight indices have a significant association with macrosomia. There was no correlation between maternal leptin and birth weight. Pregnant women should be counselled on optimal weight indices before and during pregnancy. Preconception care will help educate the women on evidence-based interventions that should help them maintain appropriate weight as World Health Organization recommends. Early booking should also be encouraged for proper counselling, dietary interventions and follow up.

Ethics approval and consent to participate

Ethical approval was obtained from the Institutional review board before commencement of the study and the participants gave consent for participation in the study before recruitment for the study.

Consent for publication consent for publication was obtained in the course of the stud

Availability of data and materials: Data is available from the corresponding author on request.

Competing interests: Authors declare no conflict of interest.

Funding: The study was funded by the authors

Authors' contributions: The work was conceived by MII and UA, while all the authors contributed to the study design. Data collection was done by MII, CNPM, CO and GU. Data analysis was done by MII with input from CNPM. The initial manuscript was drafted by MII with input from CNPM and ZO. The initial draft was edited by GU, OU HO and AU. All the authors approved the final manuscript.

Acknowledgements

The authors acknowledge the staff of Department of Obstetrics and Gynaecology , Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State for their support during the study.

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No competing interests reported.

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You are reading this latest preprint version

Antepartum maternal weight indices, Maternal Serum Leptin and Birth Weight: A cross-sectional comparative study

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Version 1

Abstract

Figures

INTRODUCTION

SUBJECTS AND METHODS

HUMAN LEPTIN ASSAY METHODOLOGY

5.8 DATA ANALYSIS

RESULTS

DISCUSSION

CONCLUSION AND RECOMMENDATIONS

Declarations

References

Additional Declarations

Status:

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