Maternal Obesity and the Risk of Infant Death in the United States A Case-Control study using the 1988 MISH data

Aimin Chen, Shingairai A. Feresu, Cristina Fernandez, and Walter J. Rogan Published in January, 2009.

Abhishek Dave Oluwaseum Oluwo Rajrupa Ghosh

Maternal obesity – Pre-pregnancy BMI ≥ 30 kg/m2

Prevalence rate in Westernized countries up to 30% Maternal obesity increases the risk of gestational hypertension,

preeclampsia, gestational diabetes, macrosomia, dystocia, labor induction, CS and PPH

Results from previous studies: Increased risk of mortality up to 18months in preterm babies

born to obese mothers. (Lucas et al) Risk of infant death doubled in obese women. (Baeten et al)

Excessive gestational weight gain, occurs in up to 40% of pregnancies

Optimal weight gain in pregnancy related to pre –pregnancy BMI Associated with:

Large for gestational age fetus Caesarean delivery Gestational diabetes mellitus

Association of maternal obesity with increased risk of infant death may be part of a continuum from reduced fertility, miscarriage and stillbirth.

Obesity in pregnancy associated with metabolic disturbances- dyslipidemia, hyperinsulinemia, elevated leptin concentrations and low grade inflammatory response.

Paucity of research on effects of obesity on neonatal and post neonatal death separately.

Lack of research into causes of infant death associated with maternal obesity

Most studies have not accounted for weight gain during pregnancy.

To determine the association between pre pregnancy BMI and risk of neonatal and post neonatal deaths.

To determine the association between weight gain in pregnancy and neonatal and post neonatal deaths.

Case control study Using the 1998 MISH data, conducted by the National Center for

Health Statistics to study factors related to poor pregnancy outcome.

MISH characteristics-Stratified systematic sampling : 9953 women with live infants 3309 with late fetal deaths 5532 who had infant deaths Data obtained post-partum from questionnaires and medical

records

Inclusion criteria- Infant deaths and live births. Study sample- Cases-5330. Controls- 7938 Cases- Infant death; Neonatal death – death within 28days of birth. Post neonatal death- death after 28days but before 1 year Controls- Live birth alive and older than 1year as at time of

interview. Exposure-Pre pregnancy BMI and pregnancy weight gain –

Obtained using self reported and recorded prepregnancy weight, weight before delivery and height.

Excluded data included- 364 women with extreme BMIs (<15kg/m2 or >45kg/m2) 1124 women with missing gestational age 222 women with GA <20weeks or >45 weeks.

Final Sample size- 7293 controls 4265 Cases ( 2667 neonatal, 1598 post neonatal)

Maternal Pre pregnancy BMI Kg/ m2 (WHO classification) –

Underweight- <18.5 Normal- 18.5- 24.9 Overweight- 25-29.9 Obese- ≥ 30

Weight gain during Pregnancy- Weight gain/ gestational weeks (Kg/wk)

<0.15, 0.15- 0.29, 0.30 – 0.44, ≥0.45

ICD-9 to group causes of neonatal and post- neonatal deaths into broad categories.

Race

Maternal age at pregnancy

Maternal education

Maternal smoking during pregnancy

Child’s sex

Live birth order;

and plurality

Multiple logistic regression models using SAS 9.1

Risk estimates using SUDAAN to derive estimates based on sampling weights of each individual.

Interaction for Pre pregnacy BMI and weight gain during pregnancy tested.

Separate analysis conducted with recorded pre pregnacy BMI

Analysis performed after excluding women with DM and hypertension.

Mothers of cases had higher percentage of pre pregnancy obesity (8.8%) compared to controls (5.9%)

They were more often African American and younger than 20 years than controls and also smoked more often.

Infants who died were more often male(57%,52%), higher birth order live birth =>3 (30%, 25%), part of multiple birth(10%, 2%), with reported birth defects (11%, 1%), LBW (56%, 6%) & preterm birth (55%, 9%)

Mothers of cases had higher percentage of (16%) weight gain <0.15 kg/week than mothers of controls who had only 8% percentage of weight gain less than 0.15 kg/week (here higher % of low weight gain were representative of women with BMI<18.5 )

TABLE 1 CONT..

RESULTS

Obese women had highest % of weight gain <0.15-0.29kg/wk and lowest % of weight gain >=0.45 kg/wk

Median weight gain by obese women was 0.23 kg/wk compared to 0.35 kg/wk by normal weight women

Without considering weight gain during pregnancy, obese women had higher risk of infant death compared to normal weight women

Underweight women also had higher risk of infant death and overweight women had marginal risk

Now Considering weight gain with BMI

Obese women had higher risk of infant death in all weight gain categories when compared to normal weight women with reference weight gain of 0.30-0.44 kg/wk

Infant death risk according to different BMI women & weight gain

Underweight women- lowest weight gain highest risk

Overweight women- lowest weight gain highest risk, but highest gain also increased risk, a reversed J shape

Obese women- highest weight gain highest risk, J shaped association

Effect of BMI and weight gain were readily evident on neonatal death, but less precise & weaker for post neonatal

In a multinomial logistic regression model, overall pattern of pre pregnancy and weight gain effect differed for neonatal and post neonatal death by X² test (p<0.01)

OR of pre pregnancy BMI and weight gain without any covariate adjustment were only slightly higher than reported

No major change in final result by adjusting for multivitamin use, marital status, breast feeding status, participation in federally funded welfare Women and Infant nutrition programs

Subsample of only singleton births or without birth defects gave similar results

What are the causes of infant death associated with obesity?

Obesity at all weight gain categories was assoc. with higher death risk from maternal pregnancy, labor, and delivery complications, short gestation and unspecified LBW

Among all, obese women with highest weight gain were assoc. with all the causes of neonatal death

4308 women with prenatal medical record , maternal obesity was also assoc. with higher risk infant deaths similar to self reported data, but was less precise

In these women with medical records, correlation coefficient of self reported pre pregnancy BMI and weight gain were respectively 0.89 & 0.55

Exclusion of women with DM & HT didn’t change risk estimate of maternal obesity & weight gain categories (data not shown)

Women with or without medical record didn’t differ in BMI and weight gain categories (data not shown)

Obese women with medical records had same results as table on next slide when BMI and weight gain were measured at 14 and 28 weeks

Is maternal pre pregnancy obesity associated with increased risk of infant death?

This study suggest that pre pregnancy obesity was highly associated with increased risk of neonatal and total infant death, but weakly to post neonatal death

This women had pregnancy complication or disorders relating to short gestation & LBW that lead to infant death

Weight gain during pregnancy modified the effect of maternal pre pregnancy BMI

What is different in this study than previous studies?

This study focuses on neonatal & post neonatal death separately

Took into account not only nulliparous but found adverse effect of obesity in parous women

Study found effects also on infants who were not preterm or LBW

The results of pre pregnancy obesity and risk of infant death were similar to previous studies if weight gain during pregnancy is not taken into account

Previous studies did not find association between pregnancy weight gain and risk of infant mortality but they explained it was because of large proportion of women had missing information on weight gain

In addition to increased infant mortality, risk for large & SGA, Preeclampsia, cesarean section needs to be considered in obese women

Obese women may need to avoid excessive weight gain, but in non obese women very low weight gain may lead to increased infant mortality

There is an ongoing discussion on optimal weight gain for obese women that leads to healthy infant. According to Kiel DW et al. 2007, no or limited weight gain has favorable pregnancy outcomes in obese women.

Results of this study needs to be confirmed in other studies as this study also has some limitations in it

Is it Biologically Plausible that maternal obesity increases the risk of infant mortality?

Risk of Infant mortality may be part of a continuum from reduced fertility, miscarriage and still birth

Maternal obesity may increase risk for gestational diabetes, hypertension, preeclampsia, macrosomia, dystocia, labor induction, cesarean section, PPH & also increased risk of birth defects and decreased women who breast feed

Obese mothers may have abnormal metabolic profile like dyslipidemia, hyperinsulinemia, elevated leptin, low grade inflammatory response

Excluding gestational HT and diabetes, risk estimate of obesity is changed only slightly partly due to underreporting of these complication or they may represent only a small proportion of obesity related problems.

STRENGTHS

The data was nationally representative and results generalizable

The sample size was big enough to ensure sufficient power to the study for relatively rare outcomes such as post neonatal death

Neonatal and post-neonatal death were separately measured

The data used in the study was quite old.

There were possibilities of recall bias and residual confounding

Not enough information was available on pregnancy complications, labor, delivery, and neonatal conditions

There may be error in the causes of infant deaths

Sample Size: Large enough to provide adequate power to the study

Generalizability: The study was generalizable. However as the data is quite old there may have been a change in race/ethnicity among the population over time

Study Design: The study design was appropriate. However, there was potential for misclassification

Confounding: The potential confounders were accounted for. However, child’s sex was unlikely to be a true confounder

Measurement of Exposures & Outcomes :Weight gain was measured per week which may not be the optimal way of measuring weight gain during pregnancy

Study question : Association between obese pre-pregnancy BMI, excess weight gain per trimester of pregnancy and infant mortality over a 3 year period (2014-2017) in St. Josephs Hospital, Bryan Texas.

Method : Study design: Prospective Cohort study. Follow up for 1 year

Objectives: To study infant mortality trends with changes in pre-pregnancy BMI and weight gain in each trimester of pregnancy

Exposure: Obese Pre-pregnancy BMI (BMI > 30 Kg/m2) Weight gain per trimester. Measured at 13, 26 weeks and before

delivery. This will fill the gap in literature by providing evidence as to which trimester was linked to major weight gain during pregnancy

Outcome: Infant Death, both neonatal & post-neonatal death would be measured. The death from domestic accidents and infectious diseases after 1 month of birth would be excluded

Strengths of the study : Temporality can be assessed Misclassification of exposure status less likely Multiple outcomes can be studied

Confounders: The confounders to be accounted for will be race, maternal

education, maternal age at pregnancy, maternal smoking during pregnancy and ART (Assisted Reproductive Technology)

Potential Biases: • Selection Bias

Gaillard, R, Felix, J F, Duijts, L, et al. (2014). Childhood consequences of maternal obesity and excessive weight gain during pregnancy. Acta obstetricia et gynecologica Scandinavica, 93(11), 1085-9.