If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, and Dr Liu)Department of Obstetrics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China (Drs Lin, Fan, Li, Chen, Zhou, and Rao, Ms Ye, Ms Wang, Ms Feng, Ms Lu, Ms Luo, and Dr Liu)
There is limited evidence regarding optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus.
OBJECTIVE
This study aimed to examine the association between gestational weight gain and perinatal outcomes among women with gestational diabetes mellitus and twin pregnancies and to explore the gestational weight gain targets by prepregnancy body mass index category.
STUDY DESIGN
A national population-based cohort study of twin pregnancies with gestational diabetes mellitus was conducted between 2014 and 2020. Women with gestational diabetes mellitus aged between 18 and 45 years with live-born twins without congenital malformations between 24 and 42 weeks of gestation were included in the analysis. Two approaches were used to determine the optimal gestational weight gain targets by body mass index category: an interquartile range method to calculate targets in low-risk gestational diabetes mellitus pregnancies and a logistic model method to identify the odds ratio targets at which a composite adverse outcome decreased.
RESULTS
Of 29,308 women with gestational diabetes mellitus and twin pregnancies, 8239 (28.1%) were normal-weight, 7626 (26.0%) were overweight, and 13,443 (45.9%) were obese. The continuous standardized gestational weight gain by 36 weeks was associated with preterm birth <36 weeks, large-for-gestational-age infants, small-for-gestational-age infants, and gestational hypertensive disorders. The interquartile range targets were 13.6 to 20.9 kg, 10.9 to 20.4 kg, and 7.7 to 17.7 kg for normal-weight, overweight, and obese women, respectively. The odds ratio targets were 14.1 to 20.0 kg, 12.1 to 16.0 kg, and 6.1 to 12.0 kg for normal-weight, overweight, and obese women, respectively. Gestational weight gain outside these targets was associated with preterm birth <36 weeks, large-for-gestational-age and small-for-gestational-age infants, and gestational hypertensive disorders, and exhibited significant population attributable fractions for preterm birth <36 weeks, large-for-gestational-age infants, and gestational hypertensive disorders across body mass index categories.
CONCLUSION
Compared with the Institute of Medicine guidelines, more stringent gestational weight gain targets would be beneficial for improved perinatal outcomes in women with gestational diabetes mellitus and twin pregnancies.
The evidence regarding optimal gestational weight gain (GWG) for women with twin pregnancies and gestational diabetes mellitus (GDM) is limited.
Key findings
In a population-based cohort study of 29,308 women with GDM and twin pregnancies, the GWG targets (interquartile range target and odds ratio target) by 2 approaches were found to be lower than the 2009 Institute of Medicine (IOM) guidelines. The targets showed advantages in eliminating adverse perinatal outcomes over the IOM guidelines in women with GDM and twin pregnancies.
What does this add to what is known?
In twin pregnancies with GDM, stricter GWG targets than the IOM guidelines are beneficial for improved perinatal outcomes.
Introduction
Gestational diabetes mellitus (GDM) is a common pregnancy-related complication affecting >20 million women worldwide.
Diabetes in Pregnancy Working GroupMaternal Medicine Clinical Study GroupRoyal College of Obstetricians and Gynaecologists, UK Gestational diabetes: opportunities for improving maternal and child health.
This complication is associated with a range of adverse perinatal outcomes in mothers and their offspring, including preterm birth (PTB), pregnancy-induced hypertension, preeclampsia (PE), large for gestational age (LGA) infants, and cesarean delivery.
Maternal and neonatal morbidity for women who would be added to the diagnosis of GDM using IADPSG criteria: a secondary analysis of the hyperglycemia and adverse pregnancy outcome study.
Maternal gestational diabetes mellitus and the risk of subsequent pediatric cardiovascular diseases of the offspring: a population-based cohort study with up to 18 years of follow up.
Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: a population-based cohort study.
A systematic review of outcomes of maternal weight gain according to the Institute of Medicine recommendations: birthweight, fetal growth, and postpartum weight retention.
Association between gestational weight gain and perinatal outcomes among twin gestations based on the 2009 Institute of Medicine (IOM) guidelines: a systematic review.
J Matern Fetal Neonatal Med.2021; ([Epub ahead of print])
Nutritional counseling can be advised during pregnancy, especially for overweight and obese women, and measures for weight control should be the primary treatment after a diagnosis of GDM. In 2009, the American Institute of Medicine (IOM) released revised recommendations for GWG by maternal body mass index (BMI) category.
Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Weight Gain During Pregnancy: Reexamining the Guidelines. Rasmussen KM, Yaktine AL, editors. Washington (DC): National Academies Press (US); 2009. PMID: 2066950
Considering the lack of GDM-specific GWG guidelines, the IOM recommendations are the only guidelines for glycemic control with lifestyle modifications for women with GDM.
Adherence to clinical practice guideline recommendations in women with gestational diabetes and associations with maternal and infant health-a cohort study.
Inadequate weight gain according to the Institute of Medicine 2009 guidelines in women with gestational diabetes: frequency, clinical predictors, and the association with pregnancy outcomes.
Twin pregnancies are more complicated than singleton pregnancies, given that twin gestations have a higher nutritional demand and an inherent nature of slower fetal growth. In this regard, diet control to maintain an optimal GWG is more challenging in twin pregnancies with GDM. The current IOM recommendations for twin pregnancies are regarded as provisional because they are derived from a single study on women with twins with an average weight ≥2500 g at term (16.8–24.5 kg for normal weight, 14.1–22.7 kg for overweight, and 11.3–19.1 kg for obesity of any class).
Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Weight Gain During Pregnancy: Reexamining the Guidelines. Rasmussen KM, Yaktine AL, editors. Washington (DC): National Academies Press (US); 2009. PMID: 2066950
Previous studies on singletons have reported that the IOM guidelines were not applicable for pregnancies with GDM and suggested the necessity of developing GDM-specific GWG targets.
Effect of pre-gestational weight and gestational weight gain in women with gestational diabetes controlled with medication on pregnancy outcomes - is recommended weight gain too liberal?.
However, according to our literature search, there is limited evidence for twin pregnancies with GDM.
Therefore, this study aimed to evaluate the association between GWG and perinatal outcomes and explore GWG targets among women with GDM and twin pregnancies.
Materials and Methods
Study design and population
This was a population-based study of women with GDM and twin pregnancies in the United States based on natality data from the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention. The deidentified public data included demographic and health data for live births based on information abstracted from birth certificates. The NCHS assumed responsibility for the ethical clearance of data collection and publication. In the present study, the data of twins delivered between January 2014 and December 2020 by mothers with GDM were used for analysis. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.
we developed an algorithm to match one twin with the other, achieving twin pairs based on the variables regarding parental characteristics and maternal outcomes (Supplemental Methods). Among the matched twin pairs (n=770,756), we excluded pregnancies with newborns having the listed congenital anomalies or death at the time of recording (n=21,814); missing information on GWG and maternal BMI (n=31,772); maternal age <18 years or >45 years (n=8992); unknown gestational age or gestational age at birth <24 weeks or >42 weeks (n=2416); and missing information on the outcomes of interest (n=11,570). Among the twin pairs with complete data, mothers without GDM or with preexisting diabetes mellitus (n=635,100) were excluded. In this study, underweight women with GDM (n=403) were also excluded because of the small sample size and the lack of IOM recommendations for underweight women (Figure 1).
Figure 1Selection of eligible records
Lin. Optimal gestational weight gain in twin pregnancy with gestational diabetes mellitus. Am J Obstet Gynecol MFM 2022.
Assessment of body mass index and gestational weight gain
Maternal prepregnancy BMI was calculated on the basis of self-reported prepregnancy height and weight and categorized on the basis of the World Health Organization recommendations as underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obesity (≥30.0).
Centers for Disease Control and Prevention, National Center for Health Statistics. Birth edit specifications for the 2003 proposed revision of the U.S. standard certificate of birth. Updated July 2012. Accessed June 6, 2022. Available at: https://www.cdc.gov/nchs/data/dvs/birth-edit-specifications.pdf
In the original data, women who did not gain weight or lost weight were recorded as 0 kg in the variable of “wtgain.” The main exposure variable was standardized GWG equivalent to 36 weeks of gestational age obtained by dividing the total weight gain by the weeks of gestation and multiplying 36. The secondary exposure was the GWG status, which was classified as adequate GWG (aGWG), inadequate GWG (iGWG), and excessive GWG (eGWG), according to the targets in this study or the IOM recommendations for the 3 BMI categories.
Definition of covariates
Maternal race and ethnicity were grouped as non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and others. Parity was classified as multiparous and nulliparous according to the total number of births. Mode of conception was classified as spontaneous, use of fertility-enhancing drugs for ovulation induction, and/or by intrauterine insemination and assisted reproductive technology (eg, in vitro fertilization, gamete intrafallopian transfer, and zygote intrafallopian transfer). Smoking status was classified as nonsmokers and smokers (before and/or during pregnancy). Because of missing information on chorionicity, we used combined neonatal sex (male-male, female-female, and male-female) as a proxy, which could be considered suboptimal.
Pregnancies with missing information on the covariates were categorized as an unknown group.
Outcomes of interest
The primary individual outcomes in this study were PTB before 36 weeks (PTB <36 weeks) and LGA infants, and the secondary outcomes included small-for-gestational-age (SGA) infants, gestational hypertensive disorders (GHDs), neonatal intensive care unit (NICU) admission, and neonatal respiratory morbidity. PTB <36 weeks was determined by the variable “obstetric estimate” of the infants’ gestation in the data, which combines the last menstrual period with ultrasound confirmation and is considered an accurate estimate.
because uncomplicated monochorionic twins can be delivered around 36 weeks. LGA and SGA infants were determined on the basis of the sex-specific birthweight reference for US twins from a previous study.
GHDs included pregnancy-induced hypertension and PE. NICU admission was defined on the basis of the reporting of admission to the NICU in the database. Neonatal respiratory morbidity was defined as need for assisted ventilation immediately or use of surfactant after birth. The composite outcome was defined as the occurrence of the aforementioned individual outcomes (PTB <36 weeks, LGA and SGA infants, GHDs, NICU admission, and respiratory morbidity).
Determination of gestational weight gain targets for women with gestational diabetes mellitus and twin pregnancies
In this study, the GWG targets by BMI category (normal weight, overweight, and obesity) were determined using 2 approaches. The first approach was based on a population with GDM that did not experience any adverse outcomes of interest. These GWG targets, called interquartile range (IQR) targets, were calculated as the IQR of total weight gain of the low-risk subgroup. The second approach was used to determine the thresholds of standardized GWG with the lowest risk of the composite outcome. These targets, called odds ratio (OR) targets, comprised all standardized GWG groups at 2.0-kg intervals with a significantly decreased adjusted OR (AOR, <1.0; P<.05) and those with nonsignificant AORs (P>.05), but between 2 groups with significantly decreased AORs, on the basis of logistic regression models adjusted for confounders.
LifeCycle Project-Maternal Obesity and Childhood Outcomes Study Group Association of gestational weight gain with adverse maternal and infant outcomes.
Women with ≤0 kg GWG were considered a separate group in the analysis, and extreme standardized GWG groups were combined for stable results in case of an insufficient number of events, where available.
Statistical analyses
Multivariable logistic regression models were used to evaluate the association of the individual outcomes with continuous standardized GWG by BMI category. These models were adjusted for maternal age, race and ethnicity, smoking status, parity, prepregnancy hypertension, mode of conception, and combined neonatal sex. For neonatal outcomes (NICU admission and neonatal respiratory morbidity), generalized estimating equation models with binomial distribution and logit link were used to address the intertwin correlation, and the gestational age at birth was included for adjustment. For neonatal respiratory morbidity, maternal use of steroids was further included for adjustment. The predicted probability of the individual outcomes was calculated and modeled with continuous standardized GWG as restricted cubic splines with 4 knots set at default positions.
On the basis of the GWG targets of this study and the IOM targets, multivariable logistic models were used to evaluate the effect of iGWG and eGWG on the outcomes, with aGWG serving as the reference. The AORs based on different GWG targets were compared using Z tests (IQR vs IOM targets and OR vs IOM targets). On the basis of the logistic models, the population attributable fractions (PAFs) were calculated using the “punaf” postestimation user-written command developed by Roger Newson in Stata software.
The PAF indicates the proportion of cases that could be prevented if the risk factor were eliminated. In this study, we were interested in the extent to which the GWG targets or the IOM targets reduce adverse perinatal outcomes. Therefore, the PAFs for aGWG were calculated, representing the proportion of cases eliminated in the population if all women gain a certain amount of weight within these GWG targets. The 95% confidence intervals were estimated using a symmetrizing complementary logarithmic transformation of the PAFs.
All statistical analyses were performed using Stata, version 17.0 (StataCorp, College Station, TX). All P values were 2-tailed, and P values <.05 were considered statistically significant.
Results
Baseline characteristics of the study population
A total of 29,308 women with GDM and twin pregnancies were eligible for the study (Figure 1), among which 8239 (28.1%) were classified as normal weight, 7626 (26.0%) as overweight, and 13,443 (45.9%) as obese. The mean maternal age was 32.2±5.2 years. Most of the women were non-Hispanic White (16,127, 55.0%), multiparous (24,530, 83.7%), nonsmokers (27,008, 92.2%), and conceived spontaneously (23,541, 80.3%). The mean gestational age at delivery was 35.3±2.4 weeks, with an overall incidence of PTB <36 weeks of 41.7%. The overall incidence of GHDs was 20.6%. Among the 58,616 newborns, the mean birthweight was 2425±549 g, with 8.2% of the newborns classified as SGA and 13.4% as LGA. A total of 24,256 (41.4%) newborns were admitted to NICU, and 10,132 (17.3%) had respiratory morbidity (Table).
TableCharacteristics and outcomes of eligible twin pregnancies with gestational diabetes mellitus
Lin. Optimal gestational weight gain in twin pregnancy with gestational diabetes mellitus. Am J Obstet Gynecol MFM 2022.
Variable
Total (n=29,308)
Normal weight (n=8239)
Overweight (n=7626)
Obesity (n=13,443)
Maternal age (y)
32.2±5.2
32.7±5.1
32.6±5.1
31.7±5.3
Race and ethnicity
Non-Hispanic White
16,127 (55.0)
4680 (56.8)
4045 (53.0)
7402 (55.1)
Non-Hispanic Black
3585 (12.2)
505 (6.1)
834 (10.9)
2246 (16.7)
Non-Hispanic Asian
3258 (11.1)
1703 (20.7)
997 (13.1)
558 (4.2)
Hispanic
5151 (17.6)
1065 (12.9)
1457 (19.1)
2629 (19.6)
Others
1187 (4.1)
286 (3.5)
293 (3.8)
608 (4.5)
Parity
Multiparous
24,530 (83.7)
6486 (78.7)
6412 (84.1)
11,632 (86.5)
Nulliparous
4661 (15.9)
1714 (20.8)
1189 (15.6)
1758 (13.1)
Unknown
117 (0.4)
39 (0.5)
25 (0.3)
53 (0.4)
Mode of conception
Spontaneous
23,541 (80.3)
6163 (74.8)
6061 (79.5)
11,317 (84.2)
Fertility-enhancing drug treatment for OI and/or IUI
1612 (5.5)
507 (6.2)
407 (5.3)
698 (5.2)
Assisted reproductive technology
3842 (13.1)
1449 (17.6)
1067 (14)
1326 (9.9)
Unknown
313 (1.1)
120 (1.5)
91 (1.2)
102 (0.8)
Smoking status
Nonsmoker
27,008 (92.2)
7758 (94.2)
7105 (93.2)
12,145 (90.3)
Smoked during or before pregnancy
2116 (7.2)
433 (5.3)
487 (6.4)
1196 (8.9)
Unknown
184 (0.6)
48 (0.6)
34 (0.5)
102 (0.8)
Prepregnancy hypertension
Yes
1635 (5.6)
133 (1.6)
291 (3.8)
1211 (9.0)
No
27,673 (94.4)
8106 (98.4)
7335 (96.2)
12,232 (91.0)
Fetal sex combination
Male-male
9472 (32.3)
2751 (33.4)
2537 (33.3)
4184 (31.1)
Female-female
9195 (31.4)
2677 (32.5)
2405 (31.5)
4113 (30.6)
Male-female
10,641 (36.3)
2811 (34.1)
2684 (35.2)
5146 (38.3)
GHDs
Yes
6048 (20.6)
1273 (15.5)
1425 (18.7)
3350 (24.9)
No
23,260 (79.4)
6966 (84.6)
6201 (81.3)
10,093 (75.1)
Gestational age at delivery (wk)
35.3±2.4
35.4±2.3
35.4±2.4
35.2±2.5
PTB <36 wk
Yes
12,233 (41.7)
3333 (40.5)
3080 (40.4)
5820 (43.3)
No
17,075 (58.3)
4906 (59.6)
4546 (59.6)
7623 (56.7)
Birthweight (g)
2425±549
2373±516
2419±536
2461±573
Growth for gestational age
SGA
4782 (8.2)
1639 (10.0)
1305 (8.6)
1838 (6.8)
AGA
45,967 (78.4)
13,523 (82.1)
12,181 (79.9)
20,263 (75.4)
LGA
7867 (13.4)
1316 (8.0)
1766 (11.6)
4785 (17.8)
NICU admission
Yes
24,256 (41.4)
6696 (40.6)
6119 (40.1)
11,441 (42.6)
No
34,360 (58.6)
9782 (59.4)
9133 (59.9)
15,445 (57.5)
Neonatal respiratory morbidity
Yes
10,132 (17.3)
2572 (15.6)
2496 (16.4)
5064 (18.8)
No
48,484 (82.7)
13,906 (84.4)
12,756 (83.6)
21,822 (81.2)
AGA, appropriate for gestational age; GHD, gestational hypertensive disorder; IUI, intrauterine insemination; LGA, large for gestational age; NICU, neonatal intensive care unit; OI, ovulation induction; PTB, preterm birth; SGA, small for gestational age.
Association between gestational weight gain and adverse outcomes
The associations between adverse perinatal outcomes and standardized GWG by BMI category are shown in Figure 2. PTB <36 weeks demonstrated a U-shaped association with GWG across BMI categories. The predicted probability of LGA infants escalated with increasing GWG, whereas that of SGA infants decreased. For GHDs, the predicted probability exhibited a J-shaped association in the normal-weight group but increased monotonically in the overweight and obesity groups. Regarding neonatal outcomes, there was no significant change in the predicted probability of NICU admission and respiratory morbidity with standardized GWG across BMI categories.
Figure 2Absolute risk of the individual perinatal outcomes with standardized GWG by BMI category
Lin. Optimal gestational weight gain in twin pregnancy with gestational diabetes mellitus. Am J Obstet Gynecol MFM 2022.
BMI, body mass index; GHD, gestational hypertensive disorder; GWG, gestational weight gain; LGA, large for gestational age; NICU, neonatal intensive care unit; PTB, preterm birth; RM, respiratory morbidity; SGA, small for gestational age.
Determination of the optimal gestational weight gain
There were 8674 women with GDM in the low-risk subgroup, including 2756 normal-weight, 2390 overweight, and 3528 obese women. The IQR targets by 36 weeks of gestation were 13.6 to 20.9 kg, 10.9 to 20.4 kg, and 7.7 to 17.7 kg for normal-weight, overweight, and obese women with twin pregnancies affected by GDM, respectively. On the basis of the multivariable logistic regression models regarding the composite outcome, significantly decreased AORs were observed at 14.1 to 20.0 kg for normal-weight women, at 12.1 to 16.0 kg for overweight women, and at 6.1 to 12.0 kg for obese women with GDM (Figure 3; Table S2). Compared with the IOM targets, both GWG targets were lower in all BMI categories (Table S1).
Figure 3Association between the composite outcome and standardized GWG groups by BMI category
Lin. Optimal gestational weight gain in twin pregnancy with gestational diabetes mellitus. Am J Obstet Gynecol MFM 2022.
Gestational weight gain status and perinatal outcomes
The Supplemental Figure depicts the distribution of GWG status based on the GWG targets of this study and the IOM targets. The association of iGWG and eGWG with the individual outcomes was evaluated by multivariable logistic regression models, and the AORs based on different GWG targets were compared visually by forest plots (Figure 4). In the normal-weight and overweight groups, both iGWG and eGWG based on the IOM target were not associated with an increased rate of PTB <36 weeks. This indicated that normal-weight and overweight women adhering to the IOM targets did not experience a reduced risk of PTB <36 weeks. In contrast, iGWG and eGWG based on the IQR and OR targets were associated with increased PTB <36 weeks. Significant differences were observed in these AORs between the GWG targets of this study and the IOM targets. In the obesity group, the AOR of iGWG based on the OR target was significantly higher than that based on the IOM target. The eGWG based on the OR target was not associated with PTB <36 weeks, whereas eGWG according to the IOM and the IOM target was associated with PTB <36 weeks. With each target, iGWG was associated with an increased rate of SGA infants, and eGWG was associated with LGA infants and GHDs, across BMI categories. Regarding the neonatal outcomes, neither iGWG nor eGWG was associated with NICU admission and respiratory morbidity.
Figure 4Association between the individual perinatal outcomes and GWG status according to GWG targets by BMI category
Lin. Optimal gestational weight gain in twin pregnancy with gestational diabetes mellitus. Am J Obstet Gynecol MFM 2022.
Asterisk represents P value for the difference between adjusted odds ratios for the interquartile range/odds ratio targets and the Institute of Medicine targets; calculated using Z=-)/+).
BMI, body mass index; eGWG, excessive gestational weight gain; GHD, gestational hypertensive disorder; GWG, gestational weight gain; iGWG, inadequate gestational weight gain; LGA, large for gestational age; NICU, neonatal intensive care unit; PTB, preterm birth; RM, respiratory morbidity; SGA, small for gestational age.
On the basis of these models, we calculated the PAFs of aGWG according to the GWG targets, as shown in Table S3. Both the IQR and OR targets significantly reduced the burden of PTB <36 weeks (PAF range based on the IQR and OR targets: 4.3%–7.0% and 5.2%–10.8%, respectively), LGA infants (PAF range based on the IQR and OR targets: 5.1%–13.6% and 14.8%–18.1%, respectively), and GHDs (PAF range based on the IQR and OR targets: 6.9%–10.2% and 10.1%–13.2%, respectively) across BMI categories. In contrast, the IOM targets did not contribute to the decreased burden of LGA infants and GHDs and only reduced the burden of PTB <36 weeks in the obesity groups. None of the GWG targets contributed to a decreased burden of adverse neonatal outcomes.
Comments
Principal findings
The subject of appropriate weight gain during pregnancy among GDM-affected women is of interest in clinical and public health; however, there is limited evidence regarding twin pregnancies with GDM. On the basis of our retrospective cohort, we found that GWG was associated with perinatal outcomes, particularly PTB <36 weeks, LGA and SGA infants, and GHDs. The GWG targets calculated using 2 approaches in this study were lower than the 2009 IOM recommendations and showed advantages in reducing the adverse perinatal outcomes over the IOM targets.
Results of the study in the context of existing literature
It is well-acknowledged that iGWG is associated with an increased rate of SGA infants and PTB, whereas eGWG is associated with LGA infants and GHDs in general pregnancies.
Because the adverse effect of eGWG on LGA or macrosomia infants is more pronounced in the context of GDM, a consensus is reached that the prevention of eGWG is of utmost importance, particularly in overweight and obese women.
Currently, the IOM recommendations are the only guidelines available for glycemic control in women with GDM. Multiple studies on singleton pregnancies have reported that limited GWG, below the IOM guidelines, exerts a protective role on LGA and macrosomia infants without increasing the rate of SGA infants.
Inadequate weight gain according to the Institute of Medicine 2009 guidelines in women with gestational diabetes: frequency, clinical predictors, and the association with pregnancy outcomes.
Thereby, the IOM guidelines have been criticized as liberal for women with GDM. Several attempts have been made to develop optimal GWG ranges for women with GDM and singletons; however, the results are conflicting.
Is the gestational weight gain recommended by the National Academy of Medicine guidelines suitable for Chinese twin-pregnant women with gestational diabetes mellitus?.
found that in Chinese twin pregnancies with GDM, GWG outside the IOM targets was associated with adverse outcomes, and advocated following the guidelines for Chinese women with GDM and twin pregnancies. However, these results were not stratified by BMI category. On the basis of the current results, we did not observe an increased rate of PTB among women with GWG below and above the IOM targets in normal-weight and overweight groups, which is conflicting with the results of the U-shaped relationship between PTB and GWG. Furthermore, the results of this study revealed that limited GWG below the IOM targets was associated with a decreased rate of LGA infants and an increased rate of SGA infants across BMI categories. However, the absolute risk of SGA infants in obese women with GDM and GWG below the IOM target did not reach expected value (10%) in the general population. These results implied the need to refine GWG targets for women with GDM and twin pregnancies.
It is challenging to recommend GWG targets for women with GDM and twin pregnancies considering the delicate balance between ensured nutrition supply for appropriate growth of both fetuses and diet management for glycemic control. Dai et al
Is the gestational weight gain recommended by the National Academy of Medicine guidelines suitable for Chinese twin-pregnant women with gestational diabetes mellitus?.
implemented modified GWG targets among Chinese GDM twin pregnancies using the subtracting method (2 kg from both upper and/or lower values of IOM targets) and the IQR method. They found no differences in adverse perinatal outcomes compared with the original IOM targets. The GWG targets in this study based on different approaches were lower than those recommended by the IOM. In the post hoc analysis, we found that compared with the IOM targets, the stricter targets identified in this study had a more comprehensive ability to reduce the rates of PTB, LGA infants, and GHDs across BMI categories, which are common comorbidities in the GDM population, despite the poor ability to reduce the burden of SGA infants. The difference between these results and those of the previous study
Is the gestational weight gain recommended by the National Academy of Medicine guidelines suitable for Chinese twin-pregnant women with gestational diabetes mellitus?.
may be attributed to the heterogeneity in ethnic origin of the study population. Achieving stricter GWG targets could be more difficult in women with GDM because they usually gain more weight compared with women without GDM before glucose screening.
demonstrated that for women with GDM who have already exceeded IOM targets, the “window of opportunity” to intervene positively by preventing continuous eGWG has not passed during GDM management. Other observational studies also supported this perspective given the improved perinatal outcomes with reduced maternal weight gain after a diagnosis of GDM.
However, considering that the evidence is from singleton pregnancies, validation of the GWG targets identified in this study is warranted in a prospective twin pregnancy cohort.
Strengths and limitations
This study has several strengths. This study attempted to investigate the association between GWG and perinatal outcomes and explore the optimal GWG ranges on the basis of a large scale of women with GDM and twin pregnancies. The nationwide study population allows statistical power to calculate GWG targets by BMI category, which facilitates prenatal counseling for women with GDM and twin pregnancies. However, several limitations of this study should also be noted. First, recall bias cannot be avoided in the self-reported prepregnancy weight. Second, information on glycemic control following the diagnosis of GDM was lacking in the retrospective database, which might have affected the perinatal outcomes. Third, as mentioned previously, this study focused on GWG throughout the gestation period, whereas weight interventions are usually implemented after the diagnosis of GDM. In this regard, the current targets would be more practical if interpreted as weekly GWG and should be further validated in a prospective twin pregnancies cohort with GDM. Finally, the GWG targets could not be calculated for underweight women and could not be stratified by obesity classes because of the limited sample size.
Conclusions
GWG is associated with PTB, LGA and SGA infants, and GHDs in women with GDM and twin pregnancies. Compared with the current IOM guidelines, more stringent GWG targets would be beneficial to reduce PTB, LGA infants, and GHDs in women with GDM and twin pregnancies.
Acknowledgments
We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.
Maternal and neonatal morbidity for women who would be added to the diagnosis of GDM using IADPSG criteria: a secondary analysis of the hyperglycemia and adverse pregnancy outcome study.
Maternal gestational diabetes mellitus and the risk of subsequent pediatric cardiovascular diseases of the offspring: a population-based cohort study with up to 18 years of follow up.
Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: a population-based cohort study.
A systematic review of outcomes of maternal weight gain according to the Institute of Medicine recommendations: birthweight, fetal growth, and postpartum weight retention.
Association between gestational weight gain and perinatal outcomes among twin gestations based on the 2009 Institute of Medicine (IOM) guidelines: a systematic review.
J Matern Fetal Neonatal Med.2021; ([Epub ahead of print])
Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Weight Gain During Pregnancy: Reexamining the Guidelines. Rasmussen KM, Yaktine AL, editors. Washington (DC): National Academies Press (US); 2009. PMID: 2066950
Adherence to clinical practice guideline recommendations in women with gestational diabetes and associations with maternal and infant health-a cohort study.
Inadequate weight gain according to the Institute of Medicine 2009 guidelines in women with gestational diabetes: frequency, clinical predictors, and the association with pregnancy outcomes.
Effect of pre-gestational weight and gestational weight gain in women with gestational diabetes controlled with medication on pregnancy outcomes - is recommended weight gain too liberal?.
Centers for Disease Control and Prevention, National Center for Health Statistics. Birth edit specifications for the 2003 proposed revision of the U.S. standard certificate of birth. Updated July 2012. Accessed June 6, 2022. Available at: https://www.cdc.gov/nchs/data/dvs/birth-edit-specifications.pdf
Is the gestational weight gain recommended by the National Academy of Medicine guidelines suitable for Chinese twin-pregnant women with gestational diabetes mellitus?.
Cite this article as: Lin D, Fan D, Li P, et al. Optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus: a population-based study in the United States. Am J Obstet Gynecol MFM 2022;XX:x.ex–x.ex.
00196-3&id=gr1.jpg){kind=link}
00196-3&id=gr2.jpg){kind=link}
00196-3&id=gr3.jpg){kind=link}
00196-3&id=gr4.jpg){kind=link}