Pregnancy Outcome in Gestational Diabetes Mellitus under Treatment

Objectives: To observe pregnancy outcomes in gestational diabetes mellitus (GDM) under treatment. Methods: Pregnant mothers (N=191) diagnosed with GDM (n=91, age: 27.44±4.91yr; body mass index, BMI: 26.88±4.16 kg/m; mean±SD) on the basis of WHO 2013 criteria were compared with non-GDM (n=100, age: 26.01±4.81yr, BMI: 25.53±3.77 kg/m, mean±SD) for pregnancy outcome irrespective of gestational age. HbA1c was also measured in all mothers. Gestational hypertension, preeclampsia, premature rupture of membrane (PROM), hydramnios, recurrent urinary tract infection (UTI), recurrent moniliasis, intrauterine growth retardation (IUGR), intra uterine death (IUD), mode of delivery, birth weight, birth injury, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress syndrome (RDS), congenital anomaly were recorded at every trimester. 160 mothers (GDM=75, non-GDM=85) could be followed for outcomes to the end of pregnancy. All the GDM mothers were offered standard treatment throughout pregnancy period. Results: HbA1c was significantly higher in GDM than that in non-GDM (5.42±0.61 vs. 4.98±0.44%, mean±SD; p<0.001). Outcome events in GDM and non-GDM were: gestational hypertension3.6% vs. 2.3% (p=0.621), preeclampsia2.4% vs. 0% (p=0.150), PROM4.9% vs. 0% (p=0.037), hydramniosnone in any group, recurrent UTI12.3% vs. 4.7% (p=0.073), recurrent moniliasis0.0% vs. 2.3% (p=0.165), caesarian section85.3% vs. 72.9% (p=0.056), small for gestational age (SGA)26.4% vs. 36.7% (p=0.246), large for gestational age (LGA)1.4% vs. 0%, p=0.246, IUGR2.3 vs. 2.5% (p=0.952), neonatal hypoglycemia2.7% vs. 0.0% (p=0.130), hyperbilirubinemia12.0% vs. 11.8% (p=0.963), RDS0.0% vs. 2.4% (p=0.181) and birth injury0.0% vs. 1.2% (p=0.346), congenital anomaly4.0% vs. 1.2% (p=0.254) and abortion1.3% vs. 0.0% (p=0.286). Preterm delivery (12.0% vs. 7.1%, p=0.285) and caesarean section (85.3% vs. 72.9%, p=0.056) were more in GDM. Conclusions: Despite treatment, adverse events were relatively higher but non-significant in GDM. DOI : 10.14302/issn.2374-9431.jbd-17-1429 Corresponding author: M A Hasanat, Professor and Chairman, Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Shahbagh, Dhaka-1000, Bangladesh, e-mail: hasanatdr@yahoo.com, Phone-880-(0)1711670735 Running title: Pregnancy Outcomes of GDM on treatment


Introduction:
Gestational diabetes mellitus (GDM) is increasing among the South Asians 1,2 .Recently our 'GDM study group' of Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka has observed an alarming frequency of 36.6%GDM by WHO 1999 criteria1 and 30.0%by WHO 2013 criteria along with 5.3% diabetes in pregnancy (DIP) in another study 2 .
GDM is associated with adverse pregnancy outcomes.However, whether standard treatment at outset makes any difference is not well studied.Several studies world wide including the land mark Hyperglycemia and Adverse Pregnancy Outcome study (HAPO study) did not assess the adverse outcomes in light of this point 3 .As GDM is associated with significant metabolic alterations, increased maternal and perinatal morbidity and mortality, it is imperative to screen pregnant mothers for GDM 4 .Many studies have observed various complications of GDM without regard to the emphasis of treatment during pregnancy [5][6][7][8] .A multicenter, randomized trial observed statistically significant decrease in the relative risks of several outcomes like macrosomia, large for gestational age (LGA) and shoulder dystocia with standard treatment for GDM.Additionally the risks for perinatal mortality, neonatal intensive care admission and birth trauma were also reduced in treated women 9 .
Present study was carried out to compare adverse pregnancy outcomes between GDM mothers on treatment and mother with normal glycemic status.

Study Design:
At the time of screening oral glucose tolerance test (OGTT) as well as HbA1c were done in all recruited mothers.The GDM group received standard treatment and both the GDM and non-GDM groups were followed till delivery.Their pregnancy outcomes were recorded.were non compliant to the advices for control of glucose.

Discussion:
Our study was intended to compare the adverse outcomes in mother and infants between GDM on standard treatment with non-GDM mothers.
The study revealed that a number of maternal as well as complications with infants in GDM are higher than non-GDM.The frequency of preeclampsia and gestational hypertension were higher though not statistically significant.Similar findings were also observed by some authors though treatment was not offered in their studies 8,10 .In GDM group, 4 mothers developed premature rupture of membrane (PROM) which was statistically significant though under treatment.While few studies observed statistically significant higher frequency of PROM in GDM mothers without standard treatment, others did not 4,10 .Another study in India showed significant number of PROM among GDM mothers on treatment 11 .Spontaneous abortion was found in only one mother of GDM group which was similar to other studies 4,12 .IUD occurred in two mothers among non-GDM group which was probably due to home delivery without standard obstetric management.Recurrent UTI was more frequently found in GDM group though it was not statistically significant and seems similar to findings of another study 4 .Mothers with GDM are nine times more likely to have vaginal candidiasis as found in Ugandal mothers 13 .But interestingly our study found higher incidence of vaginal candidiasis in non-GDM mothers.
In the context of fetal outcomes neonatal hypoglycemia, hyperbilirubinemia, congenital anomalies, macrosomia were studied between two groups.The HAPO study observed continuous linear associations between hyperglycemia and hyperbilirubinemia.They found stronger association between maternal hyperglycemia with hyperbilirubinemia but weaker with neonatal hypoglycemia though HAPO included those mothers with minimal hyperglycemia without standard treatment 3 .Our study observed increased frequency of both neonatal hypoglycemia and hyperbilirubinemia in GDM mothers though statistically insignificant.Apropos with this, others also found no significant difference of neonatal hypoglycemia and hyperbilirubinemia between GDM and non-GDM groups 14,15 .On the contrary, a study in India found significantly high frequency of neonatal hypoglycemia as well as hyperbilirubinemia 16 .

Figure-2: Mode of delivery of studied subjects
The congenital malformations among offspring of women with diabetes are not uncommon 17 .In our study, 4% neonates developed congenital anomalies which were not statistically different between two groups.
Similar findings were observed in several studies conducted in Pakistan, India and Saudi Arabia 4,10,18 .
This study demonstrated that only 1.4% babies are LGA which was not statistically significant 3 .In another study high fasting plasma glucose (FPG) was strongly associated with LGA neonates and/or macrosomia, and primary cesarean section 19 .Conversely, an outcome study in Jammu region showed birth weight was not significantly higher among infants of GDM mothers with treatment 10 .
Around 12% of the deliveries in the present study were preterm though statistically insignificant and corroborated to other studies 4,20 .GDM was positively related to the higher rate of caesarean section which was shown in HAPO study 3 .Other studies in Canada, Pakistan also showed similar type of evidence 4,21 .This study showed significant number of caesarean section among the GDM mothers.But the rationality behind the caesarean section in each case was not explored.
A multicentre randomized trial concluded that even very mild alterations in glucose tolerance can result in these adverse outcomes which can be prevented by simple but aggressive control of blood sugars 22 .In this regard, all the GDM mothers were treated with lifestyle intervention as well as insulin as required.9% of our GDM mothers required insulin in addition to lifestyle intervention.Other studies showed higher percentage of insulin requirement 12,21 .Probably this lower rate of insulin requirement in our study is due to excluding mothers with DIP.It is important to mention that GDM mothers were provided with standard treatment and overall adherence to treatment was good.This might be the reason behind no significant difference of outcomes between two groups.While conducting this study on our pregnant population we confronted multiple obstacles in maintenance of good adherence to regular follow-up.
Moreover, periodic follow-up for the status control by life style and insulin (where applicable) could not be meticulously maintained owing to lack of compliance in some cases which might have influence over the outcome to some extent.This also hindered the assessment over correlation between glycemic status, compliance for treatment and pregnancy outcome.

Conclusion:
This study showed that frequency of adverse events did not differ significantly between GDM mothers and mothers with normal glycemic status.But most of the adverse events were relatively higher in GDM mothers despite standard treatment.
It was a prospective cohort study carried out during January, 2014 to August, 2015 by GDM study group of Dept. of Endocrinology, BSMMU.Pregnant mothers (N=191) recruited consecutively from GDM clinic and diagnosed with GDM (n=91, age: 27.44±4.91yr;body mass index, BMI: 26.88±4.16kg/ m2, mean±SD) on the basis of WHO 2013 criteria were compared with non-GDM (n=100, age: 26.01±4.81yr,BMI: 25.53±3.77kg/m2, mean±SD) for pregnancy outcome irrespective of gestational age.Informed written consent was taken from each of the mothers.